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Filograna, Roberta (2015) Superoxide radical dismutation as protective mechanism to hamper the progression of Parkinson's disease. [Tesi di dottorato]

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Abstract (inglese)

Abstract
Parkinson's disease (PD) is a degenerative neurological syndrome characterized by the preferential loss of dopaminergic (DAergic) neurons in the Substantia Nigra pars compacta. PD is still incurable and conventional therapies treat only symptoms to improve the quality of life. Therefore, there is a impelling need to find out new therapeutic strategies that not only provide symptomatic relief but also halt or reverse the neuronal damage hampering PD progression. Even though the pathogenesis of this disorder remains poorly understood, oxidative stress has been identified as one of the major contributors for the nigral loss in both sporadic and genetic forms of the disease. In particular, the selective vulnerability of DAergic neurons to oxidative stress might be ascribed to dopamine (DA) metabolism, which occurs in the cytosol and represents in itself a relevant pathway for superoxide radicals production. The main hypothesis of this thesis is that the inhibition of reactive oxygen species (ROS) overproduction might delay, block or prevent the degenerative process that occurs in PD patients. In this scenario, our project was addressed to study in vitro and in vivo the potential protective role of the superoxide dismutase (SOD) enzymes and SOD mimetic compounds against oxidative injury, related to PD, adopting two experimental paradigms. We focused on SODs because they exert a crucial function in cellular antioxidant defense, promoting the elimination of superoxide anion.
The first experimental paradigm was represented by the herbicide paraquat (PQ) whose mechanism of action relies on the production of oxidative stress and it is epidemiologically linked to sporadic PD. The second one, which has been used to model a familial form of PD, was based on PINK1 deficiency. Indeed, PINK1 gene mutations have been identified as cause of recessive early-onset parkinsonism. This gene encodes for a serine/threonine kinase that is involved in the mitochondrial quality control and in the regulation of cellular oxidative status.
To evaluate whether SODs might have a protective activity against PQ toxicity or PINK1 deficiency, the cytosolic and mitochondrial SODs, respectively SOD1 and SOD2, were overexpressed in the human neuroblastoma SH-SY5Y cells and in Drosophila melanogaster. In cells and flies, the overexpression of the mitochondrial isoform rescued acute PQ toxicity. The selective effect observed seems to be associated to an intrinsic mechanism of acute treatment, which strongly compromise mitochondria, increasing ROS in these organelles and promoting their fragmentation. On the contrary, in flies the cytosolic isoform ameliorated motor dysfunctions induced by a chronic PQ exposure, even when SOD1 was overexpressed exclusively into the DAergic neurons. These observations indicate that the cytosolic compartment is particularly affected by chronic PQ treatment suggesting that other oxidative processes in the cytosol of DAergic cells, such as DA metabolism, might amplify PQ-induced oxidative stress making them particularly vulnerable. In SH-SY5Y cells, PINK1 deficiency resulted in mitochondrial fragmentation. Even in this case, SODs appeared protective rescuing the phenotype. However, while SOD1 overexpression slightly reduced these mitochondrial alterations, SOD2 seemed to reverse mitochondrial fragmentation allowing the maintenance of a healthy mitochondrial network. In flies, loss of PINK1 induced a severe motor impairment, which was rescued only by the overexpression of the cytosolic isoform suggesting that the protein might be involved in other pathways that are not strictly correlated with mitochondrial functioning.
Once the beneficial activity of SODs has been demonstrated, we then investigated the therapeutic potential use of a SOD-mimetic compound, M40403. We found that the molecule was able to protect cells and flies against the oxidative damage induced by both acute and chronic PQ exposure. In addition, the SOD mimetic was effective also in PINK1 deficient cells and flies reducing, respectively, mitochondrial fragmentation and locomotor defects. Finally, M40403 administration in SOD1 and SOD2 deficient flies partially replaced the loss of both isoforms suggesting that it can act at cytosolic and mitochondrial level.
Overall, these findings demonstrate that specific SOD-mimetic compounds can be efficacious in reducing oxidative stress and should be further explored as therapeutic agents to hamper the progression of PD.
In parallel, we developed a second research line which was aimed to the characterization of two human neuroblastoma cell lines in order to identify, between them, the most reliable cellular model for PD studies.
Cellular models are largely used to study in vitro the molecular mechanisms underlying DAergic degeneration in PD. Although their use presents several advantages, cell lines do not always recapitulate morphological and neurochemical properties of DAergic neuronal cells. Considering the relevance of DA metabolism in the pathogenesis of PD, the DAergic phenotype is an important requirement. Human neuroblastoma cell lines are commonly used as models in PD research, although they are undifferentiated, do not exhibit markers of mature neurons and appear able to synthetize different neurotransmitter, in particular the catecholamines DA and noradrenaline (NA). For this reason, we studied the ability of three different agents, phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), retinoic acid (RA) and staurosporine to drive neuronal differentiation toward a DAergic phenotype in SH-SY5Y and BE(2)-M17 cells. The first cell line is largely adopted and studied, even though the phenotype acquired upon differentiation is still a debated issue. In contrast, the second one is poorly characterized and might represent a valid alternative cellular system. In this thesis, we first investigated the acquisition of neuronal-like features in terms of growth inhibition, cell morphology and neuronal markers expression. Our results indicated that staurosporine and RA were the most efficient treatments to inhibit cell growth, respectively in SH-SY5Y and BE(2)-M17. Furthermore, in both cell lines, RA and staurosporine promoted the formation a complex network of neuritic extensions and the expression of mature neuronal markers. To evaluate whether the differentiation promotes a DAergic or NAergic phenotype in these cell lines, we analyzed the expression profile of the major genes involved in DA and NA metabolism and the intracellular content of these neurotransmitters. In SH-SY5Y cells, RA and TPA induced the down-regulation of DA- and NA-related genes as well as a decrease of neurotransmitter amounts compared to undifferentiated cells, indicating the loss of the catecholaminergic phenotype. On the contrary, staurosporine treatment resulted in the up-regulation of all these genes and an increase of NA content, enhancing the NAergic phenotype. Surprisingly, in BE(2)-M17, DA and NA levels detected in undifferentiated cells were considerably more elevated than in SH-SY5Y which suggests that these cells presents a more pronounced catecholaminergic phenotype. The latter was not affected by TPA and RA treatments, which did not substantially alter gene expression and the amount of neurotransmitters. In contrast, staurosporine promoted the up-regulation of the genes involved in metabolism of DA and NA and an increase of their intracellular amounts, indicating a relevant enhancement of the observed phenotype.
These results indicate that the BE(2)-M17 cell line emerges as a new experimental model with a catecholaminergic phenotype that differs substantially from those of SH-SY5Y cells, suggesting different fields of application for the two cell lines

Abstract (italiano)

Riassunto
La malattia di Parkinson è una sindrome neurologica degenerativa, caratterizzata dalla perdita preferenziale dei neuroni dopaminergici della Substantia Nigra pars compacta. Questa patologia è attualmente incurabile e le terapie convenzionali agiscono esclusivamente sui sintomi migliorando la qualità della vita. Pertanto, è necessario identificare nuove strategie terapeutiche che non solo forniscano un efficacie trattamento della sintomatologia ma agiscano anche ritardando i danni neuronali e arrestando la progressione della malattia. Sebbene l'eziologia è tuttora sconosciuta, lo stress ossidativo sembra svolgere un ruolo chiave nella degenerazione dopaminergica sia nella forme sporadiche che familiari della patologia. In particolare, la selettiva vulnerabilità di tali neuroni allo stress ossidativo potrebbe essere associata al metabolismo della dopamina (DA), evento molecolare citosolico responsabile, esso stesso, della sovrapproduzione di specie reattive dell'ossigeno (ROS) L'ipotesi principale alla base di questa tesi è che l'inibizione della produzione di ROS possa ritardare, arrestare o prevenire il processo neurodegenerativo che si verifica nei pazienti affetti dal morbo di Parkinson. In questo scenario, il nostro progetto si propone di studiare in vitro e in vivo il potenziale ruolo protettivo delle superossido dismutasi (SOD) e di composti che ne mimano l'attività (SOD mimetici) contro i danni ossidativi, correlati a tale patologia, utilizzando due diversi paradigmi sperimentali. La scelta di studiare questi enzimi è legata alla loro funzione cellulare antiossidante, cruciale nel promuovere l'eliminazione dell'anione superossido, radicale capostipite nella produzione a valle di specie molto pi๠tossiche e reattive.
In questo studio, il primo paradigma utilizzato è l'erbicida paraquat (PQ), il cui meccanismo di tossicità si basa sulla produzione di stress ossidativo. L'esposizione cronica a tale molecola è stata correlata epidemiologicamente all'insorgenza delle forme sporadiche di Parkinson. Il secondo modello adottato si basa sulla deficienza della chinasi PINK1, responsabile di una forma familiare della malattia. Infatti, mutazioni a carico del gene PINK1 sono state identificate come causa di parkinsonismo giovanile precoce. Questa proteina sembra svolgere un ruolo chiave nel mitochondrial quality control e nella regolazione dello stress ossidativo.
Al fine di studiare la potenziale azione protettiva delle SOD contro la tossicità esercitata dal PQ o indotta dall'assenza di PINK1, l'isoforma citosolica e quella mitocondriale, rispettivamente SOD1 e SOD2, sono state sovraespresse nelle cellule di neuroblastoma umano SH-SY5Y e in Drosophila melanogaster. In vitro e in vivo, esclusivamente la sovraespressione dell'isoforma mitocondriale ha evidenziato un effetto protettivo contro l'esposizione acuta al PQ. La selettività osservata potrebbe essere associata ad un meccanismo di tossicità intrinseco dell'erbicida che, ad elevate dosi, comprometterebbe fortemente i mitocondri, aumentando la produzione di ROS in questi organelli e promuovendone la frammentazione. Al contrario, in Drososphila, l'enzima citosolico SOD1 è in grado di migliorare le performance motorie, alterate dall'esposizione cronica al PQ. Tale effetto è stato rilevato anche quando la sovraespressione era indotta esclusivamente a livello dei neuroni dopaminergici. Le nostre osservazioni indicano che in tali condizioni il compartimento citosolico potrebbe essere particolarmente compromesso, suggerendo che nei neuroni dopaminergici il citosol possa essere la sede di altri meccanismi ossidativi, tra i quali il metabolismo della DA, in grado di amplificare o esacerbare lo stress ossidativo indotto dal PQ, rendendo tali cellule particolarmente vulnerabili. In cellule SH-SY5Y, la deficienza di PINK1 ha causato un fenotipo mitocondriale caratterizzato dalla frammentazione del network di questi organelli. Anche in questo caso, le SOD hanno svolto una funzione protettiva contrastando la frammentazione mitocondriale osservata. Tuttavia, mentre la sovraespressione della SOD1 ha ridotto solo parzialmente il danno, la SOD2 è apparsa in grado di garantire il mantenimento di un corretto network mitocondriale. In Drosophila, la perdita di PINK1 promuove una severa disabilità motoria, la quale puಠessere migliorata dall'attività dell'isoforma citosolica SOD1, suggerendo che PINK1 possa essere coinvolta in altri processi molecolari non strettamente correlati col mantenimento del funzionamento mitocondriale.
Dimostrata l'azione protettiva delle SOD, abbiamo deciso di studiare il potenziale utilizzo terapeutico del SOD mimetico M40403. I risultati delle nostre analisi hanno evidenziato che tale molecola svolga un'attività antiossidante, in vitro e in vivo, proteggendo dal danno ossidativo indotto dal trattamento acuto e cronico con l'erbicida PQ. Inoltre, il composto M40403 è stato testato in modelli cellullari e animali privi di PINKI1 nei quali ha migliorato, rispettivamente, il fenotipo mitocondriale e i difetti nell'apparato locomotore. Infine la somministrazione di questo SOD mimetico in linee di Drosophila deficienti per SOD1 o SOD2, ha rivelato che la molecola possa sopperire parzialmente all'assenza di ciascun enzima, supportando l'ipotesi che possa agire sia a livello citosolico che mitocondriale.
Complessivamente, i dati ottenuti finora hanno dimostrato che l'utilizzo di specifici composti SOD mimetici, in particolare M40403, possa essere efficacie nel contrastare danni ossidativi. Questi composti dovrebbero essere ulteriormente studiati al fine di identificare un possibile agente terapeutico per la malattia di Parkinson.
Parallelamente al progetto appena descritto, ci siamo focalizzati su un seconda linea di ricerca volta alla caratterizzazione dei due linee di neuroblastoma umano al fine di definire quali, tra queste, rappresenti il modello cellulare pi๠attendibile per lo studio della malattia di Parkinson.
I modelli cellulari sono largamente utilizzati nello studio in vitro dei meccanismi molecolari alla base della degenerazione dei neuroni dopaminergici. Nonostante il loro utilizzo presenti grandi vantaggi, queste linee cellulari non sempre ricapitolano le proprietà morfologiche e neurochimiche dei suddetti neuroni. Pertanto, considerando il ruolo del metabolismo della DA nell'eziologia del morbo di Parkinson, l'acquisizione del fenotipo dopaminergico risulta essere un requisito importante. In particolare, le linee cellulari di neuroblastoma sono spesso usate come modello, nonostante siano proliferanti, non esprimano markers caratteristici dei neuroni maturi e siano in grado di sintetizzare diversi neurotrasmettitori, in particolare le catecolamine DA e noradrenalina (NA). Per queste ragioni, abbiamo studiato l'abilità di tre differenti agenti, il 12-O-tetradecanoilforbolo-13-acetato (TPA), l'acido retinoico (RA) e la staurosporina, nel guidare il differenziamento delle cellule SH-SY5Y e BE(2)-M17 verso un fenotipo dopaminergico. La prima di queste linee cellulari è ampiamente utilizzata e studiata, nonostante il fenotipo acuisito dopo il differenziamento sia ancora un argomento dibattuto. Al contrario, la seconda è stata finora poco caratterizzata e potrebbe rappresentare un valido sistema cellulare alternativo.
In questa tesi, al fine di valutare l'acquisizione delle caratteristiche neuronali, abbiamo inizialmente analizzato l'effetto indotto dai tre agenti sull'inibizione della crescita, morfologia cellulare e espressione di markers neuronali. I nostri risultati hanno dimostrato che il trattamento con staurosporina e RA siano i pi๠efficienti nell'arrestare la proliferazione cellulare rispettivamente nelle cellule SH-SY5Y e BE(2)-M17. Inoltre, in entrambe le linee, RA e staurosporina promuovono la formazione di un compresso network di ramificazioni neuritiche e l'espressione di specifici markers neuronali citoscheletrici. Per studiare l'effetto del differenziamento nell'acquisizione di un fenotipo dopaminergico o noradrenergico nei due modelli cellulari, abbiamo valutato il profilo di espressione dei geni principalmente coinvolti nella sintesi di entrambi i neurotrasmettitori e i loro contenuto intracellulare. In cellule SH-SY5Y, il trattamento con RA e TPA è risultato in grado di promuovere non solo la down-regolazione dei geni analizzati ma anche una consistente riduzione del contenuto di DA e NA, suggerendo la perdita del fenotipo catecolaminergico. Al contrario, la staurosporina ha evidenziato la capacità di up-regolare l'espressione genica degli enzimi coinvolti nella sintesi dei due neurotrasmettitori e di incrementare il contenuto di NA, amplificando il fenotipo noradrenergico di questo modello. Nella linea cellulare BE(2)-M17, i livelli di DA and NA rilevati prima del differenziamento risultano essere considerevolmente elevati rispetto a quelli misurati nelle SH-SY5Y, evidenziando che la prima abbia un fenotipo catecolaminergico molto pi๠pronunciato della seconda. Quest'ultimo non viene sostanzialmente alterato dai trattamenti con TPA e RA, mentre il differenziamento con staurosporina è nuovamente in grado di up-regolare il profilo di espressione analizzato e di promuovere un'ulteriore sintesi di DA e NA, determinando l'acquisizione di un fenotipo ulteriormente marcato.
Concludendo, i risultati di questo studio indicano che la linea BE(2)-M17 possa essere un modello sperimentale alternativo con proprietà neurochimiche differenti dalle SH-SY5Y, suggerendo l'applicazione delle due line cellulari in differenti campi di ricerca.

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Tipo di EPrint:Tesi di dottorato
Relatore:Beltramini, Mariano
Correlatore:Bisaglia, Marco
Dottorato (corsi e scuole):Ciclo 27 > scuole 27 > BIOSCIENZE E BIOTECNOLOGIE > BIOTECNOLOGIE
Data di deposito della tesi:01 Febbraio 2015
Anno di Pubblicazione:02 Febbraio 2015
Parole chiave (italiano / inglese):SOD mimetici, malattia di Parkinson/SOD mimetic compounds, Parkinson's disease
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/09 Fisiologia
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:7926
Depositato il:12 Nov 2015 09:40
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Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Abeliovich A (2014) Neurological disorders: Quality-control pathway unlocked. Nature 510: 44-45 Cerca con Google

Abreu IA, Cabelli DE (2010) Superoxide dismutases-a review of the metal-associated mechanistic variations. Biochim Biophys Acta 1804: 263-274 Cerca con Google

Adem A, Mattsson ME, Nordberg A, Pahlman S (1987) Muscarinic receptors in human SH-SY5Y neuroblastoma cell line: regulation by phorbol ester and retinoic acid-induced differentiation. Brain Res 430: 235-242 Cerca con Google

Afanas'ev I (2010) Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory, Hormesis, and TOR. Aging Dis 1: 75-88 Cerca con Google

Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson's but not incidental Lewy body disease. J Neurochem 69: 1326-1329 Cerca con Google

Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10 Suppl: S18-25 Cerca con Google

Andreassen OA, Ferrante RJ, Dedeoglu A, Albers DW, Klivenyi P, Carlson EJ, Epstein CJ, Beal MF (2001) Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol 167: 189-195 Cerca con Google

Andres D, Keyser BM, Petrali J, Benton B, Hubbard KS, McNutt PM, Ray R (2013) Morphological and functional differentiation in BE(2)-M17 human neuroblastoma cells by treatment with Trans-retinoic acid. BMC Neurosci 14: 49 Cerca con Google

Antonyuk SV, Strange RW, Marklund SL, Hasnain SS (2009) The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding. J Mol Biol 388: 310-326 Cerca con Google

Auburger G, Klinkenberg M, Drost J, Marcus K, Morales-Gordo B, Kunz WS, Brandt U, Broccoli V, Reichmann H, Gispert S, Jendrach M (2012) Primary skin fibroblasts as a model of Parkinson's disease. Mol Neurobiol 46: 20-27 Cerca con Google

Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson's disease gene therapy: success by design meets failure by efficacy. Mol Ther 22: 487-497 Cerca con Google

Batinic-Haberle I, Benov L, Spasojevic I, Fridovich I (1998) The ortho effect makes manganese(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin a powerful and potentially useful superoxide dismutase mimic. J Biol Chem 273: 24521-24528 Cerca con Google

Batinic-Haberle I, Reboucas JS, Spasojevic I (2010) Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antioxid Redox Signal 13: 877-918 Cerca con Google

Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR (2005) Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A 102: 5703-5708 Cerca con Google

Beitz JM (2014) Parkinson's disease: a review. Front Biosci (Schol Ed) 6: 65-74 Cerca con Google

Benabid AL (2003) Deep brain stimulation for Parkinson's disease. Curr Opin Neurobiol 13: 696-706 Cerca con Google

Benarroch EE (2009) Brain iron homeostasis and neurodegenerative disease. Neurology 72: 1436-1440 Cerca con Google

Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38: 515-517 Cerca con Google

Benowitz LI, Perrone-Bizzozero NI, Finklestein SP (1987) Molecular properties of the growth-associated protein GAP-43 (B-50). J Neurochem 48: 1640-1647 Cerca con Google

Beraud D, Hathaway HA, Trecki J, Chasovskikh S, Johnson DA, Johnson JA, Federoff HJ, Shimoji M, Mhyre TR, Maguire-Zeiss KA (2013) Microglial activation and antioxidant responses induced by the Parkinson's disease protein alpha-synuclein. J Neuroimmune Pharmacol 8: 94-117 Cerca con Google

Beraud D, Twomey M, Bloom B, Mittereder A, Ton V, Neitzke K, Chasovskikh S, Mhyre TR, Maguire-Zeiss KA (2011) alpha-Synuclein Alters Toll-Like Receptor Expression. Front Neurosci 5: 80 Cerca con Google

Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. J Neurochem 73: 1127-1137 Cerca con Google

Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK (2002) Glutathione, iron and Parkinson's disease. Biochem Pharmacol 64: 1037-1048 Cerca con Google

Bhaskar A, Chawla M, Mehta M, Parikh P, Chandra P, Bhave D, Kumar D, Carroll KS, Singh A (2014) Reengineering redox sensitive GFP to measure mycothiol redox potential of Mycobacterium tuberculosis during infection. PLoS Pathog 10: e1003902 Cerca con Google

Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS (1978) Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38: 3751-3757 Cerca con Google

Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101: 1371-1378 Cerca con Google

Bisaglia M, Filograna R, Beltramini M, Bubacco L (2014) Are dopamine derivatives implicated in the pathogenesis of Parkinson's disease? Ageing Res Rev 13: 107-114 Cerca con Google

Bisaglia M, Greggio E, Beltramini M, Bubacco L (2013) Dysfunction of dopamine homeostasis: clues in the hunt for novel Parkinson's disease therapies. FASEB J 27: 2101-2110 Cerca con Google

Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3: CD007176 Cerca con Google

Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8: 57-69 Cerca con Google

Blum-Degen D, Muller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 202: 17-20 Cerca con Google

Bonifati V (2012) Autosomal recessive parkinsonism. Parkinsonism Relat Disord 18 Suppl 1: S4-6 Cerca con Google

Bonifati V (2014) Genetics of Parkinson's disease--state of the art, 2013. Parkinsonism Relat Disord 20 Suppl 1: S23-28 Cerca con Google

Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299: 256-259 Cerca con Google

Borgstahl GE, Parge HE, Hickey MJ, Beyer WF, Jr., Hallewell RA, Tainer JA (1992) The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. Cell 71: 107-118 Cerca con Google

Borland MK, Trimmer PA, Rubinstein JD, Keeney PM, Mohanakumar K, Liu L, Bennett JP, Jr. (2008) Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Mol Neurodegener 3: 21 Cerca con Google

Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823: 1-10 Cerca con Google

Castello PR, Drechsel DA, Patel M (2007) Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem 282: 14186-14193 Cerca con Google

Celotto AM, Liu Z, Vandemark AP, Palladino MJ (2012) A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease. Brain Behav 2: 424-434 Cerca con Google

Chang X, Lu W, Dou T, Wang X, Lou D, Sun X, Zhou Z (2013) Paraquat inhibits cell viability via enhanced oxidative stress and apoptosis in human neural progenitor cells. Chem Biol Interact 206: 248-255 Cerca con Google

Cheung YT, Lau WK, Yu MS, Lai CS, Yeung SC, So KF, Chang RC (2009) Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology 30: 127-135 Cerca con Google

Chien WL, Lee TR, Hung SY, Kang KH, Wu RM, Lee MJ, Fu WM (2013) Increase of oxidative stress by a novel PINK1 mutation, P209A. Free Radic Biol Med 58: 160-169 Cerca con Google

Choi HS, An JJ, Kim SY, Lee SH, Kim DW, Yoo KY, Won MH, Kang TC, Kwon HJ, Kang JH, Cho SW, Kwon OS, Park J, Eum WS, Choi SY (2006) PEP-1-SOD fusion protein efficiently protects against paraquat-induced dopaminergic neuron damage in a Parkinson disease mouse model. Free Radic Biol Med 41: 1058-1068 Cerca con Google

Chu CT (2010) A pivotal role for PINK1 and autophagy in mitochondrial quality control: implications for Parkinson disease. Hum Mol Genet 19: R28-37 Cerca con Google

Church SL, Grant JW, Meese EU, Trent JM (1992) Sublocalization of the gene encoding manganese superoxide dismutase (MnSOD/SOD2) to 6q25 by fluorescence in situ hybridization and somatic cell hybrid mapping. Genomics 14: 823-825 Cerca con Google

Ciccarone V, Spengler BA, Meyers MB, Biedler JL, Ross RA (1989) Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. Cancer Res 49: 219-225 Cerca con Google

Clagett-Dame M, McNeill EM, Muley PD (2006) Role of all-trans retinoic acid in neurite outgrowth and axonal elongation. J Neurobiol 66: 739-756 Cerca con Google

Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441: 1162-1166 Cerca con Google

Cocheme HM, Murphy MP (2008) Complex I is the major site of mitochondrial superoxide production by paraquat. J Biol Chem 283: 1786-1798 Cerca con Google

Collier TJ, Kanaan NM, Kordower JH (2011) Ageing as a primary risk factor for Parkinson's disease: evidence from studies of non-human primates. Nat Rev Neurosci 12: 359-366 Cerca con Google

Collins LM, Toulouse A, Connor TJ, Nolan YM (2012) Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease. Neuropharmacology 62: 2154-2168 Cerca con Google

Constantinescu R, Constantinescu AT, Reichmann H, Janetzky B (2007) Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y. J Neural Transm Suppl: 17-28 Cerca con Google

Costa AC, Loh SH, Martins LM (2013) Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/parkin model of Parkinson's disease. Cell Death Dis 4: e467 Cerca con Google

Coune PG, Schneider BL, Aebischer P (2012) Parkinson's disease: gene therapies. Cold Spring Harb Perspect Med 2: a009431 Cerca con Google

Dagda RK, Cherra SJ, 3rd, Kulich SM, Tandon A, Park D, Chu CT (2009) Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 284: 13843-13855 Cerca con Google

Dawson TM, Ko HS, Dawson VL (2010) Genetic animal models of Parkinson's disease. Neuron 66: 646-661 Cerca con Google

Day BJ, Batinic-Haberle I, Crapo JD (1999) Metalloporphyrins are potent inhibitors of lipid peroxidation. Free Radic Biol Med 26: 730-736 Cerca con Google

Day BJ, Fridovich I, Crapo JD (1997) Manganic porphyrins possess catalase activity and protect endothelial cells against hydrogen peroxide-mediated injury. Arch Biochem Biophys 347: 256-262 Cerca con Google

de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S, Manubens-Bertran JM, Alperovitch A, Rocca WA (1997) Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson's disease. J Neurol Neurosurg Psychiatry 62: 10-15 Cerca con Google

Debattisti V, Scorrano L (2013) D. melanogaster, mitochondria and neurodegeneration: small model organism, big discoveries. Mol Cell Neurosci 55: 77-86 Cerca con Google

Dennis KE, Aschner JL, Milatovic D, Schmidt JW, Aschner M, Kaplowitz MR, Zhang Y, Fike CD (2009) NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets. Am J Physiol Lung Cell Mol Physiol 297: L596-607 Cerca con Google

Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J Neurochem 52: 381-389 Cerca con Google

Di Napoli M, Papa F (2005) M-40403 Metaphore Pharmaceuticals. IDrugs 8: 67-76 Cerca con Google

Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson's disease. J Parkinsons Dis 3: 461-491 Cerca con Google

Dobbs RJ, Charlett A, Purkiss AG, Dobbs SM, Weller C, Peterson DW (1999) Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand 100: 34-41 Cerca con Google

Doctrow SR, Huffman K, Marcus CB, Musleh W, Bruce A, Baudry M, Malfroy B (1997) Salen-manganese complexes: combined superoxide dismutase/catalase mimics with broad pharmacological efficacy. Adv Pharmacol 38: 247-269 Cerca con Google

Domingues AF, Arduino DM, Esteves AR, Swerdlow RH, Oliveira CR, Cardoso SM (2008) Mitochondria and ubiquitin-proteasomal system interplay: relevance to Parkinson's disease. Free Radic Biol Med 45: 820-825 Cerca con Google

Dooley CT, Dore TM, Hanson GT, Jackson WC, Remington SJ, Tsien RY (2004) Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J Biol Chem 279: 22284-22293 Cerca con Google

Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM (2007) Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68: 384-386 Cerca con Google

Drechsel DA, Patel M (2008) Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease. Free Radic Biol Med 44: 1873-1886 Cerca con Google

Duttaroy A, Paul A, Kundu M, Belton A (2003) A Sod2 null mutation confers severely reduced adult life span in Drosophila. Genetics 165: 2295-2299 Cerca con Google

Eisenhofer G, Kopin IJ, Goldstein DS (2004) Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 56: 331-349 Cerca con Google

Esteves AR, Swerdlow RH, Cardoso SM (2014) LRRK2, a puzzling protein: insights into Parkinson's disease pathogenesis. Exp Neurol 261: 206-216 Cerca con Google

Evans JR, Mason SL, Barker RA (2012) Current status of clinical trials of neural transplantation in Parkinson's disease. Prog Brain Res 200: 169-198 Cerca con Google

Exner N, Treske B, Paquet D, Holmstrom K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Kruger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C (2007) Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J Neurosci 27: 12413-12418 Cerca con Google

Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernandez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey J, Singleton A, Tanner C, Hardy J, Langston JW (2001) Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol 50: 293-300 Cerca con Google

Fattman CL, Schaefer LM, Oury TD (2003) Extracellular superoxide dismutase in biology and medicine. Free Radic Biol Med 35: 236-256 Cerca con Google

Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194: 7-15 Cerca con Google

Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408: 239-247 Cerca con Google

Floor E, Wetzel MG (1998) Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 70: 268-275 Cerca con Google

Franco R, Li S, Rodriguez-Rocha H, Burns M, Panayiotidis MI (2010) Molecular mechanisms of pesticide-induced neurotoxicity: Relevance to Parkinson's disease. Chem Biol Interact 188: 289-300 Cerca con Google

Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1: 515-525 Cerca con Google

Friedman A, Galazka-Friedman J, Koziorowski D (2009) Iron as a cause of Parkinson disease - a myth or a well established hypothesis? Parkinsonism Relat Disord 15 Suppl 3: S212-214 Cerca con Google

Fujioka S, Wszolek ZK (2012) Update on genetics of parkinsonism. Neurodegener Dis 10: 257-260 Cerca con Google

Furukawa Y, Torres AS, O'Halloran TV (2004) Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. EMBO J 23: 2872-2881 Cerca con Google

Gandhi S, Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012: 428010 Cerca con Google

Gandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, Downward J, Latchman DS, Tabrizi SJ, Wood NW, Duchen MR, Abramov AY (2009) PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 33: 627-638 Cerca con Google

Gaweda-Walerych K, Zekanowski C (2013) Integrated pathways of parkin control over mitochondrial maintenance - relevance to Parkinson's disease pathogenesis. Acta Neurobiol Exp (Wars) 73: 199-224 Cerca con Google

Gemma C, Vila J, Bachstetter A, Bickford PC (2007) Oxidative Stress and the Aging Brain: From Theory to Prevention. Cerca con Google

George JM (2002) The synucleins. Genome Biol 3: REVIEWS3002 Cerca con Google

Gertz B, Wong M, Martin LJ (2012) Nuclear localization of human SOD1 and mutant SOD1-specific disruption of survival motor neuron protein complex in transgenic amyotrophic lateral sclerosis mice. J Neuropathol Exp Neurol 71: 162-177 Cerca con Google

Giasson BI, Murray IV, Trojanowski JQ, Lee VM (2001) A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem 276: 2380-2386 Cerca con Google

Girotto S, Cendron L, Bisaglia M, Tessari I, Mammi S, Zanotti G, Bubacco L (2014) DJ-1 is a copper chaperone acting on SOD1 activation. J Biol Chem 289: 10887-10899 Cerca con Google

Girotto S, Sturlese M, Bellanda M, Tessari I, Cappellini R, Bisaglia M, Bubacco L, Mammi S (2012) Dopamine-derived quinones affect the structure of the redox sensor DJ-1 through modifications at Cys-106 and Cys-53. J Biol Chem 287: 18738-18749 Cerca con Google

Gispert S, Ricciardi F, Kurz A, Azizov M, Hoepken HH, Becker D, Voos W, Leuner K, Muller WE, Kudin AP, Kunz WS, Zimmermann A, Roeper J, Wenzel D, Jendrach M, Garcia-Arencibia M, Fernandez-Ruiz J, Huber L, Rohrer H, Barrera M, Reichert AS, Rub U, Chen A, Nussbaum RL, Auburger G (2009) Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One 4: e5777 Cerca con Google

Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J (2003) Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278: 43628-43635 Cerca con Google

Gomes LC, Scorrano L (2013) Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta 1833: 205-212 Cerca con Google

Good PF, Hsu A, Werner P, Perl DP, Olanow CW (1998) Protein nitration in Parkinson's disease. J Neuropathol Exp Neurol 57: 338-342 Cerca con Google

Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14: 633-643 Cerca con Google

Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 100: 4078-4083 Cerca con Google

Guzman JN, Sanchez-Padilla J, Chan CS, Surmeier DJ (2009) Robust pacemaking in substantia nigra dopaminergic neurons. J Neurosci 29: 11011-11019 Cerca con Google

Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, Surmeier DJ (2010) Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468: 696-700 Cerca con Google

Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119: 598-620 Cerca con Google

Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298-300 Cerca con Google

Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20: 145-147 Cerca con Google

Hastings TG, Zigmond MJ (1997) Loss of dopaminergic neurons in parkinsonism: possible role of reactive dopamine metabolites. J Neural Transm Suppl 49: 103-110 Cerca con Google

Herman GE (2002) Mouse models of human disease: lessons learned and promises to come. ILAR J 43: 55-56 Cerca con Google

Heumann R, Moratalla R, Herrero MT, Chakrabarty K, Drucker-Colin R, Garcia-Montes JR, Simola N, Morelli M (2014) Dyskinesia in Parkinson's disease: mechanisms and current non-pharmacological interventions. J Neurochem 130: 472-489 Cerca con Google

Hirth F (2010) Drosophila melanogaster in the study of human neurodegeneration. CNS Neurol Disord Drug Targets 9: 504-523 Cerca con Google

Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, Mulsch A, Nussbaum RL, Muller K, Drose S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis 25: 401-411 Cerca con Google

Hosamani R (2013) Acute exposure of Drosophila melanogaster to paraquat causes oxidative stress and mitochondrial dysfunction. Arch Insect Biochem Physiol 83: 25-40 Cerca con Google

Hwang O (2013) Role of oxidative stress in Parkinson's disease. Exp Neurobiol 22: 11-17 Cerca con Google

Ii K, Ito H, Tanaka K, Hirano A (1997) Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. J Neuropathol Exp Neurol 56: 125-131 Cerca con Google

Im JY, Lee KW, Junn E, Mouradian MM (2010) DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex. Neurosci Res 67: 203-208 Cerca con Google

Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MW, Bevilacqua L, Jahani-Asl A, Callaghan S, MacLaurin JG, Winklhofer KF, Rizzu P, Rippstein P, Kim RH, Chen CX, Fon EA, Slack RS, Harper ME, McBride HM, Mak TW, Park DS (2010) Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet 19: 3734-3746 Cerca con Google

Islinger M, Li KW, Seitz J, Volkl A, Luers GH (2009) Hitchhiking of Cu/Zn superoxide dismutase to peroxisomes--evidence for a natural piggyback import mechanism in mammals. Traffic 10: 1711-1721 Cerca con Google

Jagasia R, Grote P, Westermann B, Conradt B (2005) DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans. Nature 433: 754-760 Cerca con Google

Jalava A, Akerman K, Heikkila J (1993) Protein kinase inhibitor, staurosporine, induces a mature neuronal phenotype in SH-SY5Y human neuroblastoma cells through an alpha-, beta-, and zeta-protein kinase C-independent pathway. J Cell Physiol 155: 301-312 Cerca con Google

Jalava A, Heikkila J, Lintunen M, Akerman K, Pahlman S (1992) Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13 acetate (TPA). FEBS Lett 300: 114-118 Cerca con Google

Javitch JA, D'Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U S A 82: 2173-2177 Cerca con Google

Jenner P (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53 Suppl 3: S26-36; discussion S36-28 Cerca con Google

Jin K (2010) Modern Biological Theories of Aging. Aging Dis 1: 72-74 Cerca con Google

Jinek M, East A, Cheng A, Lin S, Ma E, Doudna J (2013) RNA-programmed genome editing in human cells. Elife 2: e00471 Cerca con Google

Kamel F (2013) Epidemiology. Paths from pesticides to Parkinson's. Science 341: 722-723 Cerca con Google

Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205: 143-153 Cerca con Google

Kang MJ, Gil SJ, Koh HC (2009) Paraquat induces alternation of the dopamine catabolic pathways and glutathione levels in the substantia nigra of mice. Toxicol Lett 188: 148-152 Cerca con Google

Kawamata H, Manfredi G (2010) Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space. Antioxid Redox Signal 13: 1375-1384 Cerca con Google

Kayatekin C, Cohen NR, Matthews CR (2012) Enthalpic barriers dominate the folding and unfolding of the human Cu, Zn superoxide dismutase monomer. J Mol Biol 424: 192-202 Cerca con Google

Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, Alessi DR, Knebel A, Trost M, Muqit MM (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 460: 127-139 Cerca con Google

Kelso GF, Maroz A, Cocheme HM, Logan A, Prime TA, Peskin AV, Winterbourn CC, James AM, Ross MF, Brooker S, Porteous CM, Anderson RF, Murphy MP, Smith RA (2012) A mitochondria-targeted macrocyclic Mn(II) superoxide dismutase mimetic. Chem Biol 19: 1237-1246 Cerca con Google

Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS, Mak TW (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U S A 102: 5215-5220 Cerca con Google

Kim SU, de Vellis J (2009) Stem cell-based cell therapy in neurological diseases: a review. J Neurosci Res 87: 2183-2200 Cerca con Google

Kinumi T, Kimata J, Taira T, Ariga H, Niki E (2004) Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells. Biochem Biophys Res Commun 317: 722-728 Cerca con Google

Kirby K, Hu J, Hilliker AJ, Phillips JP (2002) RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress. Proc Natl Acad Sci U S A 99: 16162-16167 Cerca con Google

Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605-608 Cerca con Google

Kitada T, Pisani A, Porter DR, Yamaguchi H, Tscherter A, Martella G, Bonsi P, Zhang C, Pothos EN, Shen J (2007) Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci U S A 104: 11441-11446 Cerca con Google

Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 16: 724-739 Cerca con Google

Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R, Burchell L, Walden H, Macartney TJ, Deak M, Knebel A, Alessi DR, Muqit MM (2012) PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2: 120080 Cerca con Google

Korecka JA, van Kesteren RE, Blaas E, Spitzer SO, Kamstra JH, Smit AB, Swaab DF, Verhaagen J, Bossers K (2013) Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One 8: e63862 Cerca con Google

Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510: 162-166 Cerca con Google

Kozak M (1986) Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44: 283-292 Cerca con Google

Krebiehl G, Ruckerbauer S, Burbulla LF, Kieper N, Maurer B, Waak J, Wolburg H, Gizatullina Z, Gellerich FN, Woitalla D, Riess O, Kahle PJ, Proikas-Cezanne T, Kruger R (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1. PLoS One 5: e9367 Cerca con Google

Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292: R18-36 Cerca con Google

Kumar H, Lim HW, More SV, Kim BW, Koppula S, Kim IS, Choi DK (2012) The role of free radicals in the aging brain and Parkinson's disease: convergence and parallelism. Int J Mol Sci 13: 10478-10504 Cerca con Google

Kume T, Kawato Y, Osakada F, Izumi Y, Katsuki H, Nakagawa T, Kaneko S, Niidome T, Takada-Takatori Y, Akaike A (2008) Dibutyryl cyclic AMP induces differentiation of human neuroblastoma SH-SY5Y cells into a noradrenergic phenotype. Neurosci Lett 443: 199-203 Cerca con Google

Kuroda Y, Mitsui T, Kunishige M, Shono M, Akaike M, Azuma H, Matsumoto T (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 15: 883-895 Cerca con Google

Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979-980 Cerca con Google

Lashuel HA, Overk CR, Oueslati A, Masliah E (2013) The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci 14: 38-48 Cerca con Google

LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ (2005) Dopamine covalently modifies and functionally inactivates parkin. Nat Med 11: 1214-1221 Cerca con Google

Le W, Sayana P, Jankovic J (2014) Animal models of Parkinson's disease: a gateway to therapeutics? Neurotherapeutics 11: 92-110 Cerca con Google

Lee MH, Hyun DH, Jenner P, Halliwell B (2001) Effect of proteasome inhibition on cellular oxidative damage, antioxidant defences and nitric oxide production. J Neurochem 78: 32-41 Cerca con Google

Lee MK, Tuttle JB, Rebhun LI, Cleveland DW, Frankfurter A (1990) The expression and posttranslational modification of a neuron-specific beta-tubulin isotype during chick embryogenesis. Cell Motil Cytoskeleton 17: 118-132 Cerca con Google

Lehmann S, Martins LM (2013) Insights into mitochondrial quality control pathways and Parkinson's disease. J Mol Med (Berl) 91: 665-671 Cerca con Google

Leli U, Cataldo A, Shea TB, Nixon RA, Hauser G (1992) Distinct mechanisms of differentiation of SH-SY5Y neuroblastoma cells by protein kinase C activators and inhibitors. J Neurochem 58: 1191-1198 Cerca con Google

Lesage S, Brice A (2012) Role of mendelian genes in "sporadic" Parkinson's disease. Parkinsonism Relat Disord 18 Suppl 1: S66-70 Cerca con Google

Lev N, Ickowicz D, Melamed E, Offen D (2008) Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology 29: 397-405 Cerca con Google

Levanon D, Lieman-Hurwitz J, Dafni N, Wigderson M, Sherman L, Bernstein Y, Laver-Rudich Z, Danciger E, Stein O, Groner Y (1985) Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J 4: 77-84 Cerca con Google

Li XP, Xie WJ, Zhang Z, Kansara S, Jankovic J, Le WD (2012) A mechanistic study of proteasome inhibition-induced iron misregulation in dopamine neuron degeneration. Neurosignals 20: 223-236 Cerca con Google

Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11: 376-381 Cerca con Google

Lin W, Kang UJ (2008) Characterization of PINK1 processing, stability, and subcellular localization. J Neurochem 106: 464-474 Cerca con Google

Liu Z, Celotto AM, Romero G, Wipf P, Palladino MJ (2012) Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis. Neurobiol Dis 45: 362-368 Cerca con Google

Loewenbruck K, Storch A (2011) Stem cell-based therapies in Parkinson's disease: future hope or current treatment option? J Neurol 258: S346-353 Cerca con Google

LoPachin RM, Jr., Saubermann AJ (1990) Disruption of cellular elements and water in neurotoxicity: studies using electron probe X-ray microanalysis. Toxicol Appl Pharmacol 106: 355-374 Cerca con Google

Lopes FM, Schroder R, da Frota ML, Jr., Zanotto-Filho A, Muller CB, Pires AS, Meurer RT, Colpo GD, Gelain DP, Kapczinski F, Moreira JC, Fernandes Mda C, Klamt F (2010) Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies. Brain Res 1337: 85-94 Cerca con Google

Lutz AK, Exner N, Fett ME, Schlehe JS, Kloos K, Lammermann K, Brunner B, Kurz-Drexler A, Vogel F, Reichert AS, Bouman L, Vogt-Weisenhorn D, Wurst W, Tatzelt J, Haass C, Winklhofer KF (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284: 22938-22951 Cerca con Google

Macarthur H, Westfall TC, Riley DP, Misko TP, Salvemini D (2000) Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock. Proc Natl Acad Sci U S A 97: 9753-9758 Cerca con Google

Machida Y, Chiba T, Takayanagi A, Tanaka Y, Asanuma M, Ogawa N, Koyama A, Iwatsubo T, Ito S, Jansen PH, Shimizu N, Tanaka K, Mizuno Y, Hattori N (2005) Common anti-apoptotic roles of parkin and alpha-synuclein in human dopaminergic cells. Biochem Biophys Res Commun 332: 233-240 Cerca con Google

Magwere T, West M, Riyahi K, Murphy MP, Smith RA, Partridge L (2006) The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127: 356-370 Cerca con Google

Mardones L, Zuniga FA, Villagran M, Sotomayor K, Mendoza P, Escobar D, Gonzalez M, Ormazabal V, Maldonado M, Onate G, Angulo C, Concha, II, Reyes AM, Carcamo JG, Barra V, Vera JC, Rivas CI (2012) Essential role of intracellular glutathione in controlling ascorbic acid transporter expression and function in rat hepatocytes and hepatoma cells. Free Radic Biol Med 52: 1874-1887 Cerca con Google

Marklund SL (1990) Expression of extracellular superoxide dismutase by human cell lines. Biochem J 266: 213-219 Cerca con Google

Masini E, Cuzzocrea S, Mazzon E, Marzocca C, Mannaioni PF, Salvemini D (2002) Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo. Br J Pharmacol 136: 905-917 Cerca con Google

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189: 211-221 Cerca con Google

Mattsson ME, Ruusala AI, Pahlman S (1984) Changes in inducibility of ornithine decarboxylase activity in differentiating human neuroblastoma cells. Exp Cell Res 155: 105-112 Cerca con Google

McCord JM (2001) Analysis of superoxide dismutase activity. Curr Protoc Toxicol Chapter 7: Unit7 3 Cerca con Google

McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA (2002) Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10: 119-127 Cerca con Google

McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38: 1285-1291 Cerca con Google

McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW (2003) Altered proteasomal function in sporadic Parkinson's disease. Exp Neurol 179: 38-46 Cerca con Google

McNaught KS, Jenner P (2001) Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neurosci Lett 297: 191-194 Cerca con Google

McNaught KS, Mytilineou C, Jnobaptiste R, Yabut J, Shashidharan P, Jennert P, Olanow CW (2002) Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J Neurochem 81: 301-306 Cerca con Google

McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P (2001) Failure of the ubiquitin-proteasome system in Parkinson's disease. Nat Rev Neurosci 2: 589-594 Cerca con Google

McNaught KS, Perl DP, Brownell AL, Olanow CW (2004) Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann Neurol 56: 149-162 Cerca con Google

Melov S, Doctrow SR, Schneider JA, Haberson J, Patel M, Coskun PE, Huffman K, Wallace DC, Malfroy B (2001) Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J Neurosci 21: 8348-8353 Cerca con Google

Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, Wes PD, Pallanck LJ, Bonini NM (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 15: 1572-1577 Cerca con Google

Meyer AJ, Dick TP (2010) Fluorescent protein-based redox probes. Antioxid Redox Signal 13: 621-650 Cerca con Google

Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: implications in disease. Free Radic Biol Med 47: 344-356 Cerca con Google

Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D, Batinic-Haberle I (2012) Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta 1822: 794-814 Cerca con Google

Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994) Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett 180: 147-150 Cerca con Google

Mogi M, Kondo T, Mizuno Y, Nagatsu T (2007) p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain. Neurosci Lett 414: 94-97 Cerca con Google

Mollace V, Iannone M, Muscoli C, Palma E, Granato T, Rispoli V, Nistico R, Rotiroti D, Salvemini D (2003) The role of oxidative stress in paraquat-induced neurotoxicity in rats: protection by non peptidyl superoxide dismutase mimetic. Neurosci Lett 335: 163-166 Cerca con Google

Moran JM, Ortiz-Ortiz MA, Ruiz-Mesa LM, Fuentes JM (2010) Nitric oxide in paraquat-mediated toxicity: A review. J Biochem Mol Toxicol 24: 402-409 Cerca con Google

Morgan B, Sobotta MC, Dick TP (2011) Measuring E(GSH) and H2O2 with roGFP2-based redox probes. Free Radic Biol Med 51: 1943-1951 Cerca con Google

Murphy CK, Fey EG, Watkins BA, Wong V, Rothstein D, Sonis ST (2008) Efficacy of superoxide dismutase mimetic M40403 in attenuating radiation-induced oral mucositis in hamsters. Clin Cancer Res 14: 4292-4297 Cerca con Google

Murphy MP (2014) Antioxidants as therapies: can we improve on nature? Free Radic Biol Med 66: 20-23 Cerca con Google

Muscoli C, Cuzzocrea S, Riley DP, Zweier JL, Thiemermann C, Wang ZQ, Salvemini D (2003) On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies. Br J Pharmacol 140: 445-460 Cerca con Google

Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183: 795-803 Cerca con Google

Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8: e1000298 Cerca con Google

Navarro-Yepes J, Zavala-Flores L, Anandhan A, Wang F, Skotak M, Chandra N, Li M, Pappa A, Martinez-Fong D, Del Razo LM, Quintanilla-Vega B, Franco R (2014) Antioxidant gene therapy against neuronal cell death. Pharmacol Ther 142: 206-230 Cerca con Google

Navarro A, Boveris A (2009) Brain mitochondrial dysfunction and oxidative damage in Parkinson's disease. J Bioenerg Biomembr 41: 517-521 Cerca con Google

Ndengele MM, Muscoli C, Wang ZQ, Doyle TM, Matuschak GM, Salvemini D (2005) Superoxide potentiates NF-kappaB activation and modulates endotoxin-induced cytokine production in alveolar macrophages. Shock 23: 186-193 Cerca con Google

Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 54: 403-414 Cerca con Google

Olanow CW, Schapira AH (2013) Therapeutic prospects for Parkinson disease. Ann Neurol 74: 337-347 Cerca con Google

Orr WC, Sohal RS (1993) Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 301: 34-40 Cerca con Google

Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4: 552-565 Cerca con Google

Pahlman S, Odelstad L, Larsson E, Grotte G, Nilsson K (1981) Phenotypic changes of human neuroblastoma cells in culture induced by 12-O-tetradecanoyl-phorbol-13-acetate. Int J Cancer 28: 583-589 Cerca con Google

Pahlman S, Ruusala AI, Abrahamsson L, Mattsson ME, Esscher T (1984) Retinoic acid-induced differentiation of cultured human neuroblastoma cells: a comparison with phorbolester-induced differentiation. Cell Differ 14: 135-144 Cerca con Google

Pahlman S, Ruusala AI, Abrahamsson L, Odelstad L, Nilsson K (1983) Kinetics and concentration effects of TPA-induced differentiation of cultured human neuroblastoma cells. Cell Differ 12: 165-170 Cerca con Google

Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279: 18614-18622 Cerca con Google

Pan-Montojo F, Reichmann H (2014) Considerations on the role of environmental toxins in idiopathic Parkinson's disease pathophysiology. Transl Neurodegener 3: 10 Cerca con Google

Parashar V, Frankel S, Lurie AG, Rogina B (2008) The effects of age on radiation resistance and oxidative stress in adult Drosophila melanogaster. Radiat Res 169: 707-711 Cerca con Google

Park J, Kim SY, Cha GH, Lee SB, Kim S, Chung J (2005) Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 361: 133-139 Cerca con Google

Park J, Kim Y, Chung J (2009) Mitochondrial dysfunction and Parkinson's disease genes: insights from Drosophila. Dis Model Mech 2: 336-340 Cerca con Google

Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441: 1157-1161 Cerca con Google

Parker WD, Jr., Boyson SJ, Parks JK (1989) Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann Neurol 26: 719-723 Cerca con Google

Peng J, Mao XO, Stevenson FF, Hsu M, Andersen JK (2004) The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway. J Biol Chem 279: 32626-32632 Cerca con Google

Peng J, Stevenson FF, Doctrow SR, Andersen JK (2005) Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra: implications for Parkinson disease. J Biol Chem 280: 29194-29198 Cerca con Google

Perfeito R, Cunha-Oliveira T, Rego AC (2012) Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease--resemblance to the effect of amphetamine drugs of abuse. Free Radic Biol Med 53: 1791-1806 Cerca con Google

Perry JJ, Hearn AS, Cabelli DE, Nick HS, Tainer JA, Silverman DN (2009) Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis. Biochemistry 48: 3417-3424 Cerca con Google

Perry JJ, Shin DS, Getzoff ED, Tainer JA (2010) The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta 1804: 245-262 Cerca con Google

Pesah Y, Pham T, Burgess H, Middlebrooks B, Verstreken P, Zhou Y, Harding M, Bellen H, Mardon G (2004) Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131: 2183-2194 Cerca con Google

Petersen SV, Olsen DA, Kenney JM, Oury TD, Valnickova Z, Thogersen IB, Crapo JD, Enghild JJ (2005) The high concentration of Arg213-->Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities. Biochem J 385: 427-432 Cerca con Google

Pezzoli G, Cereda E (2013) Exposure to pesticides or solvents and risk of Parkinson disease. Neurology 80: 2035-2041 Cerca con Google

Pfeiffer S, Schrammel A, Koesling D, Schmidt K, Mayer B (1998) Molecular actions of a Mn(III)Porphyrin superoxide dismutase mimetic and peroxynitrite scavenger: reaction with nitric oxide and direct inhibition of NO synthase and soluble guanylyl cyclase. Mol Pharmacol 53: 795-800 Cerca con Google

Pilsl A, Winklhofer KF (2012) Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson's disease. Acta Neuropathol 123: 173-188 Cerca con Google

Pletjushkina OY, Lyamzaev KG, Popova EN, Nepryakhina OK, Ivanova OY, Domnina LV, Chernyak BV, Skulachev VP (2006) Effect of oxidative stress on dynamics of mitochondrial reticulum. Biochim Biophys Acta 1757: 518-524 Cerca con Google

Poewe W (2008) Non-motor symptoms in Parkinson's disease. Eur J Neurol 15 Suppl 1: 14-20 Cerca con Google

Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105: 1638-1643 Cerca con Google

Poole AC, Thomas RE, Yu S, Vincow ES, Pallanck L (2010) The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS One 5: e10054 Cerca con Google

Prince JA, Oreland L (1997) Staurosporine differentiated human SH-SY5Y neuroblastoma cultures exhibit transient apoptosis and trophic factor independence. Brain Res Bull 43: 515-523 Cerca con Google

Priyadarshi A, Khuder SA, Schaub EA, Priyadarshi SS (2001) Environmental risk factors and Parkinson's disease: a metaanalysis. Environ Res 86: 122-127 Cerca con Google

Przedborski S, Kostic V, Jackson-Lewis V, Naini AB, Simonetti S, Fahn S, Carlson E, Epstein CJ, Cadet JL (1992) Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J Neurosci 12: 1658-1667 Cerca con Google

Purisai MG, McCormack AL, Cumine S, Li J, Isla MZ, Di Monte DA (2007) Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis 25: 392-400 Cerca con Google

Radio NM, Mundy WR (2008) Developmental neurotoxicity testing in vitro: models for assessing chemical effects on neurite outgrowth. Neurotoxicology 29: 361-376 Cerca con Google

Rappold PM, Cui M, Chesser AS, Tibbett J, Grima JC, Duan L, Sen N, Javitch JA, Tieu K (2011) Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc Natl Acad Sci U S A 108: 20766-20771 Cerca con Google

Rettig WJ, Spengler BA, Chesa PG, Old LJ, Biedler JL (1987) Coordinate changes in neuronal phenotype and surface antigen expression in human neuroblastoma cell variants. Cancer Res 47: 1383-1389 Cerca con Google

Richardson JR, Quan Y, Sherer TB, Greenamyre JT, Miller GW (2005) Paraquat neurotoxicity is distinct from that of MPTP and rotenone. Toxicol Sci 88: 193-201 Cerca con Google

Rodriguez-Rocha H, Garcia-Garcia A, Pickett C, Li S, Jones J, Chen H, Webb B, Choi J, Zhou Y, Zimmerman MC, Franco R (2013) Compartmentalized oxidative stress in dopaminergic cell death induced by pesticides and complex I inhibitors: distinct roles of superoxide anion and superoxide dismutases. Free Radic Biol Med 61: 370-383 Cerca con Google

Rosner IA, Goldberg VM, Getzy L, Moskowitz RW (1980) A trial of intraarticular orgotein, a superoxide dismutase, in experimentally-induced osteoarthritis. J Rheumatol 7: 24-29 Cerca con Google

Ross RA, Spengler BA, Biedler JL (1983) Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J Natl Cancer Inst 71: 741-747 Cerca con Google

Rothfuss O, Fischer H, Hasegawa T, Maisel M, Leitner P, Miesel F, Sharma M, Bornemann A, Berg D, Gasser T, Patenge N (2009) Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum Mol Genet 18: 3832-3850 Cerca con Google

Rugarli EI, Langer T (2012) Mitochondrial quality control: a matter of life and death for neurons. EMBO J 31: 1336-1349 Cerca con Google

Runkel ED, Liu S, Baumeister R, Schulze E (2013) Surveillance-activated defenses block the ROS-induced mitochondrial unfolded protein response. PLoS Genet 9: e1003346 Cerca con Google

Saccon RA, Bunton-Stasyshyn RK, Fisher EM, Fratta P (2013) Is SOD1 loss of function involved in amyotrophic lateral sclerosis? Brain 136: 2342-2358 Cerca con Google

Salvemini D, Riley DP, Cuzzocrea S (2002) SOD mimetics are coming of age. Nat Rev Drug Discov 1: 367-374 Cerca con Google

Salvemini D, Wang ZQ, Zweier JL, Samouilov A, Macarthur H, Misko TP, Currie MG, Cuzzocrea S, Sikorski JA, Riley DP (1999) A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats. Science 286: 304-306 Cerca con Google

Samai M, Sharpe MA, Gard PR, Chatterjee PK (2007) Comparison of the effects of the superoxide dismutase mimetics EUK-134 and tempol on paraquat-induced nephrotoxicity. Free Radic Biol Med 43: 528-534 Cerca con Google

Samaranch L, Lorenzo-Betancor O, Arbelo JM, Ferrer I, Lorenzo E, Irigoyen J, Pastor MA, Marrero C, Isla C, Herrera-Henriquez J, Pastor P (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain 133: 1128-1142 Cerca con Google

Scherz-Shouval R, Elazar Z (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36: 30-38 Cerca con Google

Scorrano L (2013) Keeping mitochondria in shape: a matter of life and death. Eur J Clin Invest 43: 886-893 Cerca con Google

Seto NO, Hayashi S, Tener GM (1990) Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life-span. Proc Natl Acad Sci U S A 87: 4270-4274 Cerca con Google

Shamoto-Nagai M, Maruyama W, Kato Y, Isobe K, Tanaka M, Naoi M, Osawa T (2003) An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y cells. J Neurosci Res 74: 589-597 Cerca con Google

Shiba-Fukushima K, Imai Y, Yoshida S, Ishihama Y, Kanao T, Sato S, Hattori N (2012) PINK1-mediated phosphorylation of the Parkin ubiquitin-like domain primes mitochondrial translocation of Parkin and regulates mitophagy. Sci Rep 2: 1002 Cerca con Google

Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O, Suno M, Ogawa K, Hayase N, Kimura K, Shiono H (2001) Carrier-mediated processes in blood--brain barrier penetration and neural uptake of paraquat. Brain Res 906: 135-142 Cerca con Google

Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25: 302-305 Cerca con Google

Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14: 3477-3492 Cerca con Google

Sofic E, Lange KW, Jellinger K, Riederer P (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci Lett 142: 128-130 Cerca con Google

Spinelli W, Sonnenfeld KH, Ishii DN (1982) Effects of phorbol ester tumor promoters and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. Cancer Res 42: 5067-5073 Cerca con Google

Stern LF, Chapman NH, Wijsman EM, Altherr MR, Rosen DR (2003) Assignment of SOD3 to human chromosome band 4p15.3-->p15.1 with somatic cell and radiation hybrid mapping, linkage mapping, and fluorescent in-situ hybridization. Cytogenet Genome Res 101: 178 Cerca con Google

Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, Federoff HJ (2008) Synuclein activates microglia in a model of Parkinson's disease. Neurobiol Aging 29: 1690-1701 Cerca con Google

Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, Turro N, Krantz D, Edwards RH, Greene LA, Zecca L (2000) Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci U S A 97: 11869-11874 Cerca con Google

Surmeier DJ (2007) Calcium, ageing, and neuronal vulnerability in Parkinson's disease. Lancet Neurol 6: 933-938 Cerca con Google

Surmeier DJ, Guzman JN, Sanchez-Padilla J, Schumacker PT (2011) The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease. Neuroscience 198: 221-231 Cerca con Google

Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ (2009) Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat Neurosci 12: 1129-1135 Cerca con Google

Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5: 213-218 Cerca con Google

Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37: 510-518 Cerca con Google

Thenganatt MA, Jankovic J (2014) Parkinson disease subtypes. JAMA Neurol 71: 499-504 Cerca con Google

Thomas KJ, McCoy MK, Blackinton J, Beilina A, van der Brug M, Sandebring A, Miller D, Maric D, Cedazo-Minguez A, Cookson MR (2011) DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet 20: 40-50 Cerca con Google

Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8: 579-591 Cerca con Google

Tse DC, McCreery RL, Adams RN (1976) Potential oxidative pathways of brain catecholamines. J Med Chem 19: 37-40 Cerca con Google

Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433-446 Cerca con Google

Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7: 65-74 Cerca con Google

Uversky VN, Li J, Fink AL (2001) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure. J Biol Chem 276: 44284-44296 Cerca con Google

Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304: 1158-1160 Cerca con Google

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39: 44-84 Cerca con Google

Vina J, Borras C, Abdelaziz KM, Garcia-Valles R, Gomez-Cabrera MC (2013) The free radical theory of aging revisited: the cell signaling disruption theory of aging. Antioxid Redox Signal 19: 779-787 Cerca con Google

Wang D, Qian L, Xiong H, Liu J, Neckameyer WS, Oldham S, Xia K, Wang J, Bodmer R, Zhang Z (2006) Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila. Proc Natl Acad Sci U S A 103: 13520-13525 Cerca con Google

Wang X, Michaelis EK (2010) Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci 2: 12 Cerca con Google

Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147: 893-906 Cerca con Google

Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E, Muscoli C, Mollace V, Ndengele M, Ischiropoulos H, Salvemini D (2004) A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther 309: 869-878 Cerca con Google

Weihofen A, Ostaszewski B, Minami Y, Selkoe DJ (2008) Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Hum Mol Genet 17: 602-616 Cerca con Google

Weihofen A, Thomas KJ, Ostaszewski BL, Cookson MR, Selkoe DJ (2009) Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48: 2045-2052 Cerca con Google

Weinreb O, Mandel S, Youdim MB, Amit T (2013) Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators. Free Radic Biol Med 62: 52-64 Cerca con Google

White KE, Humphrey DM, Hirth F (2010) The dopaminergic system in the aging brain of Drosophila. Front Neurosci 4: 205 Cerca con Google

Whitworth AJ, Theodore DA, Greene JC, Benes H, Wes PD, Pallanck LJ (2005) Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Proc Natl Acad Sci U S A 102: 8024-8029 Cerca con Google

Whitworth AJ, Wes PD, Pallanck LJ (2006) Drosophila models pioneer a new approach to drug discovery for Parkinson's disease. Drug Discov Today 11: 119-126 Cerca con Google

Wicks S, Bain N, Duttaroy A, Hilliker AJ, Phillips JP (2009) Hypoxia rescues early mortality conferred by superoxide dismutase deficiency. Free Radic Biol Med 46: 176-181 Cerca con Google

Winklhofer KF (2014) Parkin and mitochondrial quality control: toward assembling the puzzle. Trends Cell Biol 24: 332-341 Cerca con Google

Wispe JR, Clark JC, Burhans MS, Kropp KE, Korfhagen TR, Whitsett JA (1989) Synthesis and processing of the precursor for human mangano-superoxide dismutase. Biochim Biophys Acta 994: 30-36 Cerca con Google

Wood-Kaczmar A, Gandhi S, Yao Z, Abramov AY, Miljan EA, Keen G, Stanyer L, Hargreaves I, Klupsch K, Deas E, Downward J, Mansfield L, Jat P, Taylor J, Heales S, Duchen MR, Latchman D, Tabrizi SJ, Wood NW (2008) PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS One 3: e2455 Cerca con Google

Wu S, Zhou F, Zhang Z, Xing D (2011) Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission-fusion proteins. FEBS J 278: 941-954 Cerca con Google

Wu XF, Block ML, Zhang W, Qin L, Wilson B, Zhang WQ, Veronesi B, Hong JS (2005) The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid Redox Signal 7: 654-661 Cerca con Google

Xie HR, Hu LS, Li GY (2010) SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chin Med J (Engl) 123: 1086-1092 Cerca con Google

Yang W, Chen L, Ding Y, Zhuang X, Kang UJ (2007) Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice. Hum Mol Genet 16: 2900-2910 Cerca con Google

Yang W, Tiffany-Castiglioni E (2007) The bipyridyl herbicide paraquat induces proteasome dysfunction in human neuroblastoma SH-SY5Y cells. J Toxicol Environ Health A 70: 1849-1857 Cerca con Google

Yang W, Tiffany-Castiglioni E (2008) Paraquat-induced apoptosis in human neuroblastoma SH-SY5Y cells: involvement of p53 and mitochondria. J Toxicol Environ Health A 71: 289-299 Cerca con Google

Yang W, Tiffany-Castiglioni E, Lee MY, Son IH (2010) Paraquat induces cyclooxygenase-2 (COX-2) implicated toxicity in human neuroblastoma SH-SY5Y cells. Toxicol Lett 199: 239-246 Cerca con Google

Yang Y, Gehrke S, Imai Y, Huang Z, Ouyang Y, Wang JW, Yang L, Beal MF, Vogel H, Lu B (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A 103: 10793-10798 Cerca con Google

Yokochi M (1997) Familial juvenile parkinsonism. Eur Neurol 38 Suppl 1: 29-33 Cerca con Google

Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A 93: 2696-2701 Cerca con Google

Youle RJ, Karbowski M (2005) Mitochondrial fission in apoptosis. Nat Rev Mol Cell Biol 6: 657-663 Cerca con Google

Young IS, Woodside JV (2001) Antioxidants in health and disease. J Clin Pathol 54: 176-186 Cerca con Google

Zahid M, Saeed M, Yang L, Beseler C, Rogan E, Cavalieri EL (2011) Formation of dopamine quinone-DNA adducts and their potential role in the etiology of Parkinson's disease. IUBMB Life 63: 1087-1093 Cerca con Google

Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5: 863-873 Cerca con Google

Zecca L, Zucca FA, Albertini A, Rizzio E, Fariello RG (2006) A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease. Neurology 67: S8-11 Cerca con Google

Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154: 1423-1429 Cerca con Google

Zhou C, Huang Y, Shao Y, May J, Prou D, Perier C, Dauer W, Schon EA, Przedborski S (2008) The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc Natl Acad Sci U S A 105: 12022-12027 Cerca con Google

Zhou ZD, Refai FS, Xie SP, Ng SH, Chan CH, Ho PG, Zhang XD, Lim TM, Tan EK (2014) Mutant PINK1 upregulates tyrosine hydroxylase and dopamine levels, leading to vulnerability of dopaminergic neurons. Free Radic Biol Med 68: 220-233 Cerca con Google

Zimmermann M, Gardoni F, Marcello E, Colciaghi F, Borroni B, Padovani A, Cattabeni F, Di Luca M (2004) Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines. J Neurochem 90: 1489-1499 Cerca con Google

Ziviani E, Tao RN, Whitworth AJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A 107: 5018-5023 Cerca con Google

Ziviani E, Whitworth AJ (2010) How could Parkin-mediated ubiquitination of mitofusin promote mitophagy? Autophagy 6: 660-662 Cerca con Google

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