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Agostini, Mario (2017) Exploring Orai2 function in alzheimer's disease models based on presenilin 2 and amyloid precursor protein mutants. [Tesi di dottorato]

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Abstract (inglese)

Alzheimer'™s disease (AD) is the most common form of dementia among elderly population. More than twenty years ago the so-called amyloid hypothesis was formulated based on the major histopathological hallmarks of AD, among which the amyloid plaques are the most known and studied. This hypothesis was prompted by the discovery of three genes that, whereas mutated, are associated with the familial forms of the disease (FAD). One of these genes encodes for the amyloid precursor protein (APP), a single-pass type I transmembrane protein that undergoes sequential cleavages operated by the secretase family of enzymes. The last and key secretase, called gamma-secretase, is composed of four proteins, among which we found either presenilin 1 (PS1) or presenilin 2 (PS2), encoded by other two genes (PSEN1/PSEN2) that are responsible for FAD pathogenesis. Autosomic dominant mutations in either APP, PSEN1 or PSEN2 cause accelerated Abeta deposition due to an increased Abeta42/Abeta40 ratio. While the vast majority of AD cases are sporadic, FAD patients bearing PS2 mutations show a clinical course much similar to that of sporadic patients.
By many groups it was found that PSs are capable of perturbing cellular Ca2+ homeostasis, and, particularly, our group demonstrated that PS2, either bearing FAD-linked mutations or wild-type (WT), lowers endoplasmic reticulum (ER) and Golgi apparatus Ca2+ content, interacts with SERCA pump, dampening its function, and tethers ER and mitochondria; all of these pleiotropic effects are independent of its gamma-secretase activity. Recently another group identified PS2 as a regulator of the ER Ca2+ content, together with Orai2, a plasma membrane channel implicated in the Store-Operated Ca2+ Entry (SOCE). This latter phenomenon is impaired in AD, and specifically it is down-tuned in mutant PS-bearing cells. Taken together this body of information offered an interesting background to study the interplay between ER Ca2+ levels, SOCE defects and APP processing/Abeta production. Taking advantage of the PS2-based AD mouse models available in our laboratory, namely the homozygous single transgenic (TG) line expressing the FAD-linked mutant PS2-N141I (line PS2.30H) and the homozygous double transgenic (2TG) line expressing PS2-N141I together with the Swedish double mutant APP-K670M/N671L (line B6.152H), we could investigate the expression pattern of Orai2 in the nervous tissue.
Western blot analyses on cortices and hippocampi revealed that Orai2 was overexpressed in cortices from TG and 2TG mice, when compared to C57BL/6 (WT) mice. This overexpression was mainly due to the neuronal contribution since it was even higher in cortical neuronal cultures and in situ Orai2 was found only in neurons, as assayed by immunohistochemical analysis of brain slices. Orai2 up-regulation, that is the condition found in TG and 2TG neurons, is capable of perturbing cellular Ca2+ homeostasis. Particularly, when overexpressed it caused a significant decrease in IP3-induced ER Ca2+ release in both H4-APPswe and HEK29T cells; these results are consistent with a decreased ER Ca2+ level, as measured with the ER-targeted probe G-CEPIA1er. In addition to this, Orai2 revealed to be a less efficient mediator of SOCE than Orai1, since it dampened SOCE when overexpressed alone and it produced a much smaller SOCE when overexpressed with STIM1 as compared with Orai1 plus STIM1 overexpression. Conversely to our expectations, Orai2 downregulation had a noticeable effect neither on IP3-induced ER Ca2+ release nor on total store Ca2+ content; it however improved Ca2+ entry upon store depletion. As far as subcellular localization goes, Orai2 overexpression did not increase the fraction of protein present in the ER and it appeared that most of the protein was found at the early endosomal level, as revealed by immunofluorescence staining of various subcellular compartments. This holds true moving to cortical neurons, where Orai2 was preferentially found in Rab5-EEA1 positive endosomes in primary cultures from WT mice, with a dramatic accumulation at this level in neurons from 2TG mice, possibly reflecting the increased early-endosome compartment that characterizes the AD phenotype. Orai2 localization is, however, dynamic, meaning that it moves in and out of endosomes when properly stimulating neurons with compounds able to induce neuronal activity or to stimulate SOCE. This behaviour is anyway different among the three genotypes, with TG neurons showing a greater tendency to retrieve Orai2 in endosomes upon cell stimulation, and 2TG neurons being unable to properly tune their endosome pool, possibly because of its higher accumulation level. Whether these changes involve also Orai1 has still to be evaluated and it will give us a better picture of this unknown phenomenon. Finally, evidence is provided that a down-tuning of SOCE is associated with increased levels of secreted Abeta42, as measured by ELISA performed on conditioned media from mutant APP-expressing cells such as CHO-7PA2 and H4-APPswe.

Abstract (italiano)

La malattia di Alzheimer (AD) costituisce la forma di demenza più comune nella popolazione anziana. Ormai più di vent'anni fa è stata formulata la cosiddetta ipotesi della cascata amiloide, la quale si basa sulle placche amiloidi, uno dei principali marker di AD, tra i più conosciuti e studiati. La formulazione di quest'™ipotesi fu permessa dalla scoperta di tre gene i quali, allorché mutati, sono associati con la forma familiare di AD (FAD). Uno di questi geni codifica per la proteina precursore dell'™amiloide (APP), la quale è una proteina di tipo I a singolo dominio transmembrana che viene tagliata in maniera sequenziale dagli enzimi della famiglia delle secretasi. L'™ultima secretasi a tagliare APP, nonché la più importante nell'™AD, è chiamata gamma-secretasi ed è composta da quattro proteine, che comprendono o la presenilina 1 (PS1) o la presenilina 2 (PS2), codificate dagli altri due geni (PSEN1/PSEN2) responsabili della patogenesi di FAD. Mutazioni autosomiche dominanti in APP, PSEN1 o PSEN2 causano una deposizione più veloce di Abeta dovuta ad un aumentato rapporto Abeta42/Abeta40. La maggior parte dei casi di AD, tuttavia, è sporadica; i pazienti FAD con mutazioni in PS2 mostrano un decorso clinico della malattia molto più simile a quello dei pazienti sporadici.
Molti gruppi di ricerca hanno dimostrato la capacità delle PSs di perturbare l'™omeostasi cellulare del Ca2+, e in particolare il nostro gruppo ha dimostrato che PS2, sia nella forma mutata associata a FAD che nella forma wild-type (WT), abbassa il contenuto di Ca2+ del reticolo endoplasmatico (ER) e dell'apparato di Golgi. Inoltre essa interagisce con la pompa SERCA, diminuendone il funzionamento, e modula la vicinanza fra ER e mitocondri; tutte queste funzioni pleiotropiche sono indipendenti dalla sua attività gamma-secretasica. Recentemente un altro gruppo ha identificato PS2 come un regolatore del contenuto di Ca2+ del ER, insieme ad Orai2, il quale è un canale della membrana plasmatica implicato nell'™entrata di Ca2+ dipendente dallo svuotamento del ER (SOCE). Quest'™ultimo fenomeno è alterato nell'AD, e in particolare è ridotto nelle cellule che esprimono PS mutate. Questa serie di informazioni rappresenta una base interessante per lo studio dell'™interazione fra contenuto di Ca2+ del ER, diminuzione di SOCE e metabolismo di APP/produzione di Abeta. Grazie ai modelli murini di AD basati su PS2 presenti in laboratorio, specificatamente il modello singolo transgenico (TG), esprimente il mutante FAD PS2-N141I (linea PS2.30H) e il modello doppio transgenico (2TG), esprimente PS2-N141I insieme al mutante Swedish APP-K670M/N671L (linea B6.152H), abbiamo potuto investigare il pattern di espressione di Orai2 nel tessuto nervoso.
Nei Western blot di cortecce ed ippocampi abbiamo notato come Orai2 sia sovra-espressa nella corteccia dei topi TG e 2TG se confrontati con topi di controllo C57BL/6 (WT). Quest'aumento di espressione è dovuto principalmente ad un contributo neuronale, sia in quanto è maggiore in colture neuronali pure, sia perché Orai2 è presente solamente nei neuroni in situ, come rivelato dall'analisi immunoistochimica di fettine di cervello. L'™aumentata espressione di Orai2, così come si ritrova nei neuroni TG e 2TG, è in grado di alterare l'™omeostasi cellulare del Ca2+. In particolare, quando sovra-espressa, Orai2 causa una riduzione significativa del rilascio di Ca2+ indotto da IP3, sia in cellule H4-APPswe che HEK293T; questi risultati sono in accordo con una riduzione del contenuto di Ca2+ del ER, condizione osservata utilizzando la sonda G-CEPIA1er, direzionata al ER. Inoltre, Orai2 si è rivelato essere un mediatore di SOCE meno efficiente di Orai1, infatti diminuisce SOCE quando espresso da solo e, se co-espresso con STIM1, dà vita ad un SOCE meno ampio di quello prodotto da Orai1 co-espresso con STIM1. Contrariamente a quanto atteso la riduzione di Orai2 non produce alcuna diminuzione né del rilascio di Ca2+ indotto da IP3, né del contenuto totale di Ca2+ dei depositi intracellulari; essa tuttavia produce un lieve aumento dell'™ingresso di Ca2+ causato dalla deplezione dei depositi. Per quanto riguarda la localizzazione subcellulare, la sovra-espressione di Orai2 non aumenta la frazione di questa proteina presente nel ER, la maggior parte di Orai2 è infatti presente a livello degli 'early endosomes', come dimostrato marcando numerosi compartimenti subcellulari in immunofluorescenza. Ciò resta vero anche nei neuroni corticali in coltura. Nei neuroni WT, Orai2 si trova preferenzialmente negli endosomi positivi per Rab5 ed EEA1, a questo livello la localizzazione aumenta nei neuroni 2TG, un accumulo causato probabilmente dall™aumento degli 'œearly endosomes' tipico del fenotipo AD. Nonostante sia presente a livello endosomiale, la localizzazione di Orai2 è dinamica, e cioè cambia fra dentro e fuori dagli endosomi a seconda dello stimolo usato per aumentare l'™attività neuronale o per indurre SOCE. Questo dinamismo appare diverso fra i tre genotipi, dove i neuroni TG mostrano una maggior tendenza ad accumulare Orai2 negli endosomi dopo stimolazione della cellula, mentre i neuroni 2TG risultano incapaci di modulare questo aspetto, probabilmente perché in queste cellule l'™accumulo di endosomi è prossimo alla saturazione. Resta da valutare se questi cambi di localizzazione interessano anche Orai1, un'™informazione che ci permetterà di avere un'™idea più precisa di questo fenomeno sconosciuto. Infine vi è evidenza che la diminuzione di SOCE è associata ad un aumento dei livelli di Abeta42 secreta, così come misurato tramite saggio ELISA sui terreni condizionati provenienti da cellule che esprimono una forma mutata di APP, quali le CHO-7PA2 e le H4-APPswe.

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Tipo di EPrint:Tesi di dottorato
Relatore:Fasolato, Cristina
Dottorato (corsi e scuole):Ciclo 29 > Corsi 29 > BIOSCIENZE E BIOTECNOLOGIE
Data di deposito della tesi:31 Gennaio 2017
Anno di Pubblicazione:31 Gennaio 2017
Parole chiave (italiano / inglese):calcium, alzheimer's disease, presenilin, SOCE, Orai1, Orai2
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/10 Biochimica
Area 06 - Scienze mediche > MED/04 Patologia generale
Area 05 - Scienze biologiche > BIO/09 Fisiologia
Struttura di riferimento:Centri > Centro Interdipartimentale di servizi A. Vallisneri
Dipartimenti > Dipartimento di Biologia
Codice ID:10198
Depositato il:03 Nov 2017 10:21
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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.

Adunsky, A., et al. 1991 Increased cytosolic free calcium in lymphocytes of Alzheimer patients. Journal of Neuroimmunology 33(2):167-72. Cerca con Google

Agostini, M., and C. Fasolato 2016 When, where and how? Focus on neuronal calcium dysfunctions in Alzheimer's Disease. Cell Calcium. Cerca con Google

Al-Mousa, F., and F. Michelangeli 2012 Some Commonly Used Brominated Flame Retardants Cause Ca2+-ATPase Inhibition, Beta-Amyloid Peptide Release and Apoptosis in SH-SY5Y Neuronal Cells. Plos One 7(4). Cerca con Google

Alberdi, E., et al. 2010 Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium 47(3):264-72. Cerca con Google

Alberdi, E., et al. 2013 Ca2+-dependent endoplasmic reticulum stress correlates with astrogliosis in oligomeric amyloid b-treated astrocytes and in a model of Alzheimer's disease. Aging Cell 12(2):292-302. Cerca con Google

Albrecht, T., et al. 2015 Fluorescent biosensors illuminate calcium levels whithin defined beta-cell endosome subpopulations. Cell Calcium 57(4):263-74 Cerca con Google

Albuquerque, E. X., et al. 2009 Mammalian nicotinic acetylcholine receptors: from structure to function. Physiological Reviews 89(1):73-120. Cerca con Google

Allen, D. G., J. R. Blinks, and F. G. Prendergast 1977 Aequorin luminescence:relation of light emission to calcium concentration - a calcium-independent component. Science 195:996-998. Cerca con Google

Amcheslavsky, A., et al. 2015 Molecular biophysics of Orai store-operated Ca2+ channels. Biophys J 108(2):237-46. Cerca con Google

Anderson, S., et al. 1981 Sequence and organization of the human mitochondrial genome. Nature 290(9 April 1981):457-465. Cerca con Google

Arispe, N., J. C. Diaz, and O. Simakova 2007 Ab ion channels. Prospects for treating Alzheimer's disease with Ab channel blockers. Biochimica et Biophysica Acta 1768(8):1952-65. Cerca con Google

Arispe, N., et al. 2010 Polyhistidine peptide inhibitor of the Ab calcium channel potently blocks the Ab-induced calcium response in cells. Theoretical modeling suggests a cooperative binding process. Biochemistry 49(36):7847-53. Cerca con Google

Baba, Y., et al. 2006 Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum. Proc Natl Acad Sci U S A 103(45):16704-9. Cerca con Google

Baird, G. S., D. A. Zacharias, and R. Y. Tsien 1999 Circular permutation and receptor insertion within green fluorescent proteins. Proceedings of the National Academy of Sciences of the United States of America 96(20):11241-6. Cerca con Google

Bajar, B. T., et al. 2016 A Guide to Fluorescent Protein FRET Pairs. Sensors (Basel) 16(9). Cerca con Google

Bandara, S., S. Malmersjo, and T. Meyer 2013 Regulators of calcium homeostasis identified by inference of kinetic model parameters from live single cells perturbed by siRNA. Sci Signal 6(283):ra56. Cerca con Google

Bathori, G., et al. 2006 Ca2+-dependent control of the permeability properties of the mitochondrial outer membrane and voltage-dependent anion-selective channel (VDAC). J Biol Chem 281(25):17347-58. Cerca con Google

Benfenati, V., et al. 2011 An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc Natl Acad Sci U S A 108(6):2563-8. Cerca con Google

Berna-Erro, A., et al. 2009 STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. Sci Signal 2(93):ra67. Cerca con Google

Bernardi, P., et al. 1984 Pathway for uncoupler-induced calcium efflux in rat liver mitochondria: inhibition by ruthenium red. Biochemistry 23(8):1645-51. Cerca con Google

Berridge, M. J. 1998 Neuronal calcium signaling. Neuron 21(1):13-26. Cerca con Google

- 2010 Calcium hypothesis of Alzheimer's disease. Pflügers Archiv 459(3):441-9. Cerca con Google

- 2014 Calcium regulation of neural rhythms, memory and Alzheimer's disease. The Journal of physiology 592(Pt 2):281-93. Cerca con Google

Berridge, M. J., M. D. Bootman, and H. L. Roderick 2003 Calcium signalling: dynamics, homeostasis and remodelling. Nature Reviews. Molecular Cell Biology 4(7):517-529. Cerca con Google

Berridge, M. J., P. Lipp, and M. D. Bootman 2000 The versatility and universality of calcium signalling. Nature Reviews. Molecular Cell Biology 1(1):11-21. Cerca con Google

Birnbaum, J. H., et al. 2015 Calcium flux-independent NMDA receptor activity is required for Ab oligomer-induced synaptic loss. Cell Death & Disease 6. Cerca con Google

Bojarski, L., et al. 2009 Presenilin-dependent expression of STIM proteins and dysregulation of capacitative Ca2+ entry in familial Alzheimer's disease. Biochimica et Biophysica Acta 1793(6):1050-7. Cerca con Google

Bonora, M., et al. 2013 Subcellular calcium measurements in mammalian cells using jellyfish photoprotein aequorin-based probes. Nat Protoc 8(11):2105-18. Cerca con Google

Bragadin, M., T. Pozzan, and G. F. Azzone 1979 Kinetics of Ca2+ carrier in rat liver mitochondria. Biochemistry 18(26):5972-5978. Cerca con Google

Brandman, O., et al. 2007 STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 131(7):1327-39. Cerca con Google

Brini, M. 2008 Calcium-sensitive photoproteins. Methods 46(3):160-6. Cerca con Google

Brini, M., and E. Carafoli 2009 Calcium pumps in health and disease. Physiological Reviews 89(4):1341-78. Cerca con Google

Brini, M., et al. 1995 Transfected aequorin in the measurement of cytosolic Ca2+ concentration ([Ca2+]c): a critical evaluation. The Journal of Biological Chemistry 270:9896-9903. Cerca con Google

Brunello, L., et al. 2009 Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake. Journal of Cellular and Molecular Medicine 13:3358-69. Cerca con Google

Brunkan, A. L., and A. M. Goate 2005 Presenilin function and gamma-secretase activity. Journal of Neurochemistry 93(4):769-92. Cerca con Google

Caballero, E., et al. 2016 A new procedure for amyloid b oligomers preparation enables the unambiguous testing of their effects on cytosolic and mitochondrial Ca2+ entry and cell death in primary neurons. Neuroscience Letters 612:66-73. Cerca con Google

Cahalan, M. D. 2009 STIMulating store-operated Ca2+ entry. Nature Cell Biology 11(6):669-77. Cerca con Google

Calcraft, P. J., et al. 2009 NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459(7246):596-600. Cerca con Google

Cataldo, A. M., et al. 2000 Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157(1):277-86. Cerca con Google

Catterall, W.A. 2000 Structure and regulation of voltage-gated Ca2+ channels. Annual Review of Cell and Developmental Biology 16:521-555. Cerca con Google

Ceglia, I., et al. 2015 APP intracellular domain-WAVE1 pathway reduces amyloid-beta production. Nat Med 21(9):1054-9. Cerca con Google

Chakroborty, S., et al. 2012 Stabilizing ER Ca2+ channel function as an early preventative strategy for Alzheimer's disease. PloS One 7(12):e52056. Cerca con Google

Chakroborty, S., et al. 2009 Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. The Journal of Neuroscience 29(30):9458-70. Cerca con Google

Chandra, S., et al. 1991 Calcium sequestration in the Golgi apparatus of cultured mammalian cells revealed by laser scanning confocal microscopy and ion microscopy. Journal of Cell Science 100 ( Pt 4):747-52. Cerca con Google

Chen, T. W., et al. 2013 Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499(7458):295-300. Cerca con Google

Chen, Y. R., and C. G. Glabe 2006 Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides A beta 40 and A beta 42 - Stable trimer or tetramer formation by A beta 42. Journal of Biological Chemistry 281(34):24414-24422. Cerca con Google

Cheung, K. H., et al. 2010 Gain-of-function enhancement of IP3 receptor modal gating by familial Alzheimer's disease-linked presenilin mutants in human cells and mouse neurons. Science Signaling 3(114):ra22. Cerca con Google

Cheung, K. H., et al. 2008 Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron 58(6):871-83. Cerca con Google

Chyung, J. H., D. M. Raper, and D. J. Selkoe 2005 gamma-secretase exists on the plasma membrane as an intact complex that accepts substrates and effects intramembrane cleavage. Journal of Biological Chemistry 280(6):4383-4392. Cerca con Google

Citron, M., et al. 1997 Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nature Medicine 3(1):67-72. Cerca con Google

Clapham, D. E. 2007 Calcium signaling. Cell 131(6):1047-58. Cerca con Google

Coen, K., et al. 2012 Lysosomal calcium homeostasis defects, not proton pump defects, cause endo-lysosomal dysfunction in PSEN-deficient cells. Journal of Cell Biology 198(1):23-35. Cerca con Google

Coon, A. L., et al. 1999 L-type calcium channels in the hippocampus and cerebellum of Alzheimer's disease brain tissue. Neurobiology of Aging 20(6):597-603. Cerca con Google

Costantini, L. M., et al. 2012 Assessing the tendency of fluorescent proteins to oligomerize under physiologic conditions. Traffic 13(5):643-9. Cerca con Google

Crouch, P. J., et al. 2005 Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-b1-42. Journal of Neuroscience 25(3):672-9. Cerca con Google

Csala, M., G. Banhegyi, and A. Benedetti 2006 Endoplasmic reticulum: a metabolic compartment. FEBS Lett 580(9):2160-5. Cerca con Google

De Felice, F. G., et al. 2007 Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. The Journal of Biological Chemistry 282(15):11590-601. Cerca con Google

de la Fuente, S., et al. 2013 Ca2+ homeostasis in the endoplasmic reticulum measured with a new low-Ca2+-affinity targeted aequorin. Cell Calcium 54(1):37-45. Cerca con Google

De Mario, A., et al. 2015 The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase. Frontiers in Cellular Neuroscience 9:416. Cerca con Google

De Stefani, D., M. Patron, and R. Rizzuto 2015 Structure and function of the mitochondrial calcium uniporter complex. Biochimica et Biophysica Acta 1853(9):2006-11. Cerca con Google

De Stefani, D., et al. 2011 A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. Cerca con Google

De Strooper, B. 2007 Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Report 8(2):141-6. Cerca con Google

De Strooper, B., and W. Annaert 2010 Novel Research Horizons for Presenilins and gamma-Secretases in Cell Biology and Disease. Annual Review of Cell and Developmental Biology, Vol 26 26:235-260. Cerca con Google

De Strooper, B., T. Iwatsubo, and M. S. Wolfe 2012 Presenilins and gamma-Secretase: Structure, Function, and Role in Alzheimer Disease. Cold Spring Harbor Perspectives in Medicine 2(1). Cerca con Google

De Strooper, B., and E. Karran 2016 The Cellular Phase of Alzheimer's Disease. Cell 164(4):603-15. Cerca con Google

Decker, H., et al. 2010 Amyloid-b peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3b in primary cultured hippocampal neurons. Journal of Neuroscience 30(27):9166-71. Cerca con Google

Del Prete, D., F. Checler, and M. Chami 2014 Ryanodine receptors: physiological function and deregulation in Alzheimer disease. Molecular Neurodegeneration 9:21. Cerca con Google

Demuro, A., et al. 2005 Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. The Journal of Biological Chemistry 280(17):17294-300. Cerca con Google

Demuro, A., and I. Parker 2013 Cytotoxicity of intracellular ab42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate. The Journal of Neuroscience 33(9):3824-33. Cerca con Google

Di Virgilio, F., C. Fasolato, and T. H. Steinberg 1988 Inhibitors of membrane transport system for organic anions block fura-2 excretion from PC12 and N2A cells. Biochem J 256(3):959-63. Cerca con Google

Drago, I., et al. 2008 Calcium dynamics in the peroxisomal lumen of living cells. The Journal of Biological Chemistry 283(21):14384-90. Cerca con Google

Dziewczapolski, G., et al. 2009 Deletion of the alpha7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. Journal of Neuroscience 29(27):8805-15. Cerca con Google

Edmonds, E. C., et al. 2015 Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer's Disease. Journal of Alzheimers Disease 47(1):231-242. Cerca con Google

Ertekin-Taner, N. 2007 Genetics of Alzheimer's disease: a centennial review. Neurologic Clinics 25(3):611-67, v. Cerca con Google

Espana, J., et al. 2010 b-Amyloid Disrupts Activity-Dependent Gene Transcription Required for Memory through the CREB Coactivator CRTC1. Journal of Neuroscience 30(28):9402-9410. Cerca con Google

Facchinetti, F., et al. 2006 Nimodipine selectively stimulates b-amyloid 1-42 secretion by a mechanism independent of calcium influx blockage. Neurobiology of Aging 27(2):218-227. Cerca con Google

Fasolato, C., B. Innocenti, and T. Pozzan 1994 Receptor-activated Ca2+ influx: how many mechanisms for how many channels? Trends in Pharmacological Sciences 15:77-83. Cerca con Google

Fedrizzi, L., et al. 2008 Interplay of the Ca2+-binding protein dream with presenilin in neuronal Ca2+ signaling. The Journal of Biological Chemistry. Cerca con Google

Feng, X., et al. 2014 Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and plasma membrane. J Biol Chem 289(7):4262-72. Cerca con Google

Ferreiro, E., et al. 2006 An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-b peptides neurotoxicity. Neurobiology of Disease 23(3):669-78. Cerca con Google

Feske, S., et al. 2006 A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441(7090):179-85. Cerca con Google

Filadi, R., et al. 2015 Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proceedings of the National Academy of Sciences of the United States of America 112(17):E2174-81. Cerca con Google

- 2016 Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2. Cell reports 15(10):2226-38. Cerca con Google

Florean, C., et al. 2008 High content analysis of gamma-secretase activity reveals variable dominance of presenilin mutations linked to familial Alzheimer's disease. Biochimica et Biophysica Acta 1783(8):1551-60. Cerca con Google

Fontana, R., et al. 2017 Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP. Neurobiol Aging 50:64-76. Cerca con Google

Forette, F., et al. 2002 The prevention of dementia with antihypertensive treatment. Archives of Internal Medicine 162(18):2046-2052. Cerca con Google

Forstl, H., and A. Kurz 1999 Clinical features of Alzheimer's disease. European Archives of Psychiatry and Clinical Neuroscience 249(6):288-290. Cerca con Google

Foskett, J. K., et al. 2007 Inositol trisphosphate receptor Ca2+ release channels. Physiological Reviews 87(2):593-658. Cerca con Google

Fukumori, A., et al. 2010 Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis. J Neurosci 30(23):7853-62. Cerca con Google

Gan, K. J., and M. A. Silverman 2015 Dendritic and axonal mechanisms of Ca2+ elevation impair BDNF transport in Abeta oligomer-treated hippocampal neurons. Molecular Biology of the Cell 26(6):1058-71. Cerca con Google

Gant, J. C., et al. 2006 Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-induced Ca2+ release. Journal of Neuroscience 26(13):3482-90. Cerca con Google

Giacomello, M., et al. 2005 Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer's disease presenilin-2 T122R mutation and anticipates the onset of dementia. Neurobiology of Disease 18(3):638-648. Cerca con Google

Goedert, M., and M. G. Spillantini 2006 A century of Alzheimer's disease. Science 314(5800):777-81. Cerca con Google

Green, K. N., and F. M. LaFerla 2008 Linking calcium to Abeta and Alzheimer's disease. Neuron 59(2):190-4. Cerca con Google

Greotti, E., et al. 2016 Characterization of the ER-Targeted Low Affinity Ca(2+) Probe D4ER. Sensors (Basel) 16(9). Cerca con Google

Griesbeck, Oliver, et al. 2001 Reducing the environmental sensitivity of yellow fluorescent protein. Mechanism and applications. The Journal of Biological Chemistry 276(31):29188-“29194. Cerca con Google

Grigoriev, I., et al. 2008 STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER. Curr Biol 18(3):177-82. Cerca con Google

Grynkiewicz, G., M. Poenie, and R. Y. Tsien 1985 A new generation of Ca2+ indicators with greatly improved fluorescence properties. The Journal of Biological Chemistry 260:3440-3450. Cerca con Google

Guo, X., et al. 2016 Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon. Proc Natl Acad Sci U S A 113(36):E5318-27. Cerca con Google

Haas, L. T., et al. 2016 Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease. Brain 139(Pt 2):526-46. Cerca con Google

Haass, C., and D. J. Selkoe 2007 Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid b-peptide. Nature Reviews. Molecular Cell Biology 8(2):101-12. Cerca con Google

Hanson, J. E., et al. 2015 Altered GluN2B NMDA receptor function and synaptic plasticity during early pathology in the PS2APP mouse model of Alzheimer's disease. Neurobiology of Disease 74:254-62. Cerca con Google

Hansson, C. A., et al. 2004 Nicastrin, presenilin, APH-1, and PEN-2 form active g-secretase complexes in mitochondria. The Journal of Biological Chemistry 279(49):51654-51660. Cerca con Google

Hansson Petersen, C. A., et al. 2008 The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 105(35):13145-50. Cerca con Google

Hardy, J., and D. Allsop 1991 Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends in Pharmacological Sciences 12(10):383-8. Cerca con Google

Hardy, J., and D. J. Selkoe 2002 The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297(5580):353-356. Cerca con Google

Harraz, O. F., and C. Altier 2014 STIM1-mediated bidirectional regulation of Ca(2+) entry through voltage-gated calcium channels (VGCC) and calcium-release activated channels (CRAC). Front Cell Neurosci 8:43. Cerca con Google

Hedskog, L., et al. 2013 Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models. Proceedings of the National Academy of Sciences of the United States of America 110(19):7916-21. Cerca con Google

Henze, K., and W. Martin 2003 Evolutionary biology: essence of mitochondria. Nature 426(6963):127-8. Cerca con Google

Hernandez, C. M., et al. 2010 Loss of a7 nicotinic receptors enhances b-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease. Journal of Neuroscience 30(7):2442-53. Cerca con Google

Herreman, A., et al. 2000 Total inactivation of g-secretase activity in presenilin-deficient embryonic stem cells. Nature Cell Biology 2(7):461-462. Cerca con Google

Honarnejad, K., and J. Herms 2012 Presenilins: role in calcium homeostasis. International Journal of Biochemistry & Cell Biology 44(11):1983-6. Cerca con Google

Hooper, R., B. S. Rothberg, and J. Soboloff 2014 Neuronal STIMulation at rest. Science Signaling 7(335):pe18. Cerca con Google

Horikawa, K., et al. 2010 Spontaneous network activity visualized by ultrasensitive Ca(2+) indicators, yellow Cameleon-Nano. Nat Methods 7(9):729-32. Cerca con Google

Hoth, M., and B. A. Niemeyer 2013 The neglected CRAC proteins: Orai2, Orai3, and STIM2. Curr Top Membr 71:237-71. Cerca con Google

Hou, X., et al. 2012 Crystal structure of the calcium release-activated calcium channel Orai. Science 338(6112):1308-13. Cerca con Google

Inayama, M., et al. 2015 Orai1-Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines. Cell Calcium 57(5-6):337-47. Cerca con Google

Inouye, S., et al. 1985 Cloning and sequence analysis of cDNA for the luminescent protein aequorin. Proceedings of the National Academy of Sciences of the United States of America 82(10):3154-3158. Cerca con Google

Jaworska, A., et al. 2013 Analysis of calcium homeostasis in fresh lymphocytes from patients with sporadic Alzheimer's disease or mild cognitive impairment. Biochim Biophys Acta 1833(7):1692-9. Cerca con Google

Jayadev, S., et al. 2010 Alzheimer's disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 133:1143-1154. Cerca con Google

Joseph, S. K., et al. 1997 Membrane insertion, glycosylation, and oligomerization of inositol trisphosphate receptors in a cell-free translation system. J Biol Chem 272(3):1579-88. Cerca con Google

Jurgensen, S., et al. 2011 Activation of D1/D5 dopamine receptors protects neurons from synapse dysfunction induced by amyloid-b oligomers. The Journal of Biological Chemistry 286(5):3270-6. Cerca con Google

Kaether, C., et al. 2006 Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface. Traffic 7(4):408-15. Cerca con Google

Kapur, A., et al. 1998 L-Type calcium channels are required for one form of hippocampal mossy fiber LTP. Journal of Neurophysiology 79(4):2181-90. Cerca con Google

Kar, P., et al. 2012 Different agonists recruit different stromal interaction molecule proteins to support cytoplasmic Ca2+ oscillations and gene expression. Proc Natl Acad Sci U S A 109(18):6969-74. Cerca con Google

Karran, E., M. Mercken, and B. De Strooper 2011 The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nature Reviews Drug Discovery 10(9):698-U1600. Cerca con Google

Khosravani, H., et al. 2008 Prion protein attenuates excitotoxicity by inhibiting NMDA receptors. Journal of Cell Biology 181(3):551-565. Cerca con Google

Kim, J., et al. 2007 Biogenesis of gamma-secretase early in the secretory pathway. Journal of Cell Biology 179(5):951-963. Cerca con Google

Kim, J., et al. 2014 Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release. Biophysical Journal 107(7):1601-8. Cerca con Google

Kimberly, W. T., et al. 2000 The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. Journal of Biological Chemistry 275(5):3173-3178. Cerca con Google

Kipanyula, M. J., et al. 2012a Ca2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2. Aging Cell 11(5):885-893. Cerca con Google

Kito, H., et al. 2015 Regulation of store-operated Ca2+ entry activity by cell cycle dependent up-regulation of Orai2 in brain capillary endothelial cells. Biochem Biophys Res Commun 459(3):457-62. Cerca con Google

Kraft, R. 2015 STIM and ORAI proteins in the nervous system. Channels:235-243. Cerca con Google

Krieger-Brauer, H. I., and M. Gratzl 1983 Effects of monovalent and divalent cations on Ca2+ fluxes across chromaffin secretory membrane vesicles. J Neurochem 41(5):1269-76. Cerca con Google

Kurup, P., et al. 2010 Ab-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61. Journal of Neuroscience 30(17):5948-57. Cerca con Google

Lacruz, R. S., and S. Feske 2015 Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci 1356:45-79. Cerca con Google

LaFerla, F. M. 2010 Pathways linking A beta and tau pathologies. Biochemical Society Transactions 38:993-995. Cerca con Google

LaFerla, F. M., K. N. Green, and S. Oddo 2007 Intracellular amyloid-beta in Alzheimer's disease. Nature Reviews Neuroscience 8(7):499-509. Cerca con Google

Lalonde, J., G. Saia, and G. Gill 2014 Store-operated calcium entry promotes the degradation of the transcription factor Sp4 in resting neurons. Science Signaling 7(328):ra51. Cerca con Google

Lambert, M. P., et al. 1998 Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proceedings of the National Academy of Sciences of the United States of America 95(11):6448-53. Cerca con Google

Landfield, P. W. 1994 Increased hippocampal Ca2+ channel activity in brain aging and dementia. Hormonal and pharmacologic modulation. Annals of the New York Academy of Sciences 747:351-64. Cerca con Google

Lauren, J., et al. 2009 Cellular prion protein mediates impairment of synaptic plasticity by amyloid-b oligomers. Nature 457(7233):1128-U84. Cerca con Google

Lazzari, C., et al. 2015 Ab42 oligomers selectively disrupt neuronal calcium release. Neurobiology of Aging 36(2):877-885. Cerca con Google

Leal, N. S., et al. 2016 Mitofusin-2 knockdown increases ER-mitochondria contact and decreases amyloid beta-peptide production. Journal of Cellular and Molecular Medicine. Cerca con Google

Lee, J. H., et al. 2015 Presenilin 1 Maintains Lysosomal Ca2+ Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification. Cell Reports 12(9):1430-44. Cerca con Google

Lee, J. H., et al. 2010 Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141(7):1146-58. Cerca con Google

Lee, L., P. Kosuri, and O. Arancio 2014 Picomolar amyloid-b peptides enhance spontaneous astrocyte calcium transients. Journal of Alzheimer's Disease 38(1):49-62. Cerca con Google

Leissring, M.A., et al. 2000 Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. Journal of Cell Biology 149(4):793-798. Cerca con Google

Lesne, S. E. 2014 Toxic oligomer species of amyloid-beta in Alzheimer's disease, a timing issue. Swiss medical weekly 144:w14021. Cerca con Google

Lesne, S. E., et al. 2013 Brain amyloid-b oligomers in ageing and Alzheimer's disease. Brain 136(Pt 5):1383-98. Cerca con Google

Lesne, S., et al. 2006 A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440(7082):352-7. Cerca con Google

Lewis, R. S. 2007 The molecular choreography of a store-operated calcium channel. Nature 446(7133):284-7. Cerca con Google

Li, Z., et al. 2007 Mapping the interacting domains of STIM1 and Orai1 in Ca2+ release-activated Ca2+ channel activation. J Biol Chem 282(40):29448-56. Cerca con Google

Lim, D., et al. 2016 Calcium signalling toolkits in astrocytes and spatio-temporal progression of Alzheimer's disease. Current Alzheimer Research 13(4):359-69. Cerca con Google

Liou, J., et al. 2007 Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion. Proceedings of the National Academy of Sciences of the United States of America 104(22):9301-6. Cerca con Google

Liou, J., et al. 2005 STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Current Biology 15(13):1235-41. Cerca con Google

Lissandron, V., et al. 2010 Unique characteristics of Ca2+ homeostasis of the trans-Golgi compartment. Proceedings of the National Academy of Sciences of the United States of America 107(20):9198-203. Cerca con Google

Liu, Y. T., et al. 2007 NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. Journal of Neuroscience 27(11):2846-2857. Cerca con Google

Llinas, R., J. R. Blinks, and C. Nicholson 1972 Calcium transient in presynaptic terminal of squid giant synapse: detection with aequorin. Science 176(4039):1127-9. Cerca con Google

Lombardo, S., and U. Maskos 2015 Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment. Neuropharmacology 96(Pt B):255-62. Cerca con Google

Ma, Q. H., et al. 2008 A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nature Cell Biology 10(3):283-U29. Cerca con Google

Mahapatra, N. R., et al. 2004 A dynamic pool of calcium in catecholamine storage vesicles. Exploration in living cells by a novel vesicle-targeted chromogranin A-aequorin chimeric photoprotein. The Journal of Biological Chemistry 279(49):51107-21. Cerca con Google

Manczak, M., et al. 2006 Mitochondria are a direct site of Ab accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Human Molecular Genetics 15(9):1437-49. Cerca con Google

Mank, M., et al. 2008 A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Nature Methods 5(9):805-11. Cerca con Google

Marciani, D. J. 2016 A retrospective analysis of the Alzheimer's disease vaccine progress - The critical need for new development strategies. Journal of Neurochemistry 137(5):687-700. Cerca con Google

Martell, J. D., et al. 2012 Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy. Nat Biotechnol 30(11):1143-8. Cerca con Google

McCarthy, J. V., C. Twomey, and P. Wujek 2009 Presenilin-dependent regulated intramembrane proteolysis and gamma-secretase activity. Cellular and Molecular Life Sciences 66(9):1534-1555. Cerca con Google

McLarnon, J. G., et al. 2005 Perturbations in calcium-mediated signal transduction in microglia from Alzheimer's disease patients. Journal of Neuroscience Research 81(3):426-35. Cerca con Google

Meckler, X., and F. Checler 2016 Presenilin 1 and Presenilin 2 Target gamma-Secretase Complexes to Distinct Cellular Compartments. J Biol Chem 291(24):12821-37. Cerca con Google

Meldolesi, J., and T. Pozzan 1998 The endoplasmic reticulum Ca2+ store: a view from the lumen. Trends in Biochemical Sciences 23:10-14. Cerca con Google

Mercer, J. C., et al. 2006 Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J Biol Chem 281(34):24979-90. Cerca con Google

Michikawa, T., et al. 1999 Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositol 1,4,5-trisphosphate receptor. Neuron 23(4):799-808. Cerca con Google

Minano-Molina, A. J., et al. 2011 Soluble oligomers of amyloid-b peptide disrupt membrane trafficking of a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction. The Journal of Biological Chemistry 286(31):27311-21. Cerca con Google

Minta, A., J. P. Kao, and R. Y. Tsien 1989 Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. The Journal of Biological Chemistry 264(14):8171-8. Cerca con Google

Mitchell, K. J., et al. 2001 Dense core secretory vesicles revealed as a dynamic Ca2+ store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera. The Journal of Cell Biology 155(1):41-51. Cerca con Google

Miyawaki, A., et al. 1999 Dynamic and quantitative Ca2+ measurements using improved cameleons. Proceedings of the National Academy of Sciences of the United States of America 96:2135-2140. Cerca con Google

Miyawaki, A., et al. 1997 Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388:882-887. Cerca con Google

Moccia, F., et al. 2015 Stim and Orai proteins in neuronal Ca2+ signaling and excitability. Frontiers in Cellular Neuroscience 9:153. Cerca con Google

Muik, M., et al. 2012 Ca(2+) release-activated Ca(2+) (CRAC) current, structure, and function. Cell Mol Life Sci 69(24):4163-76. Cerca con Google

Murray, D. H., et al. 2016 An endosomal tether undergoes an entropic collapse to bring vesicles together. Nature 537(7618):107-111. Cerca con Google

Nagai, T., et al. 2001 Circularly permuted green fluorescent proteins engineered to sense Ca2+. Proceedings of the National Academy of Sciences of the United States of America 98(6):3197-3202. Cerca con Google

Nagai, T., et al. 2004 Expanded dynamic range of fluorescent indicators for Ca2+ by circularly permuted yellow fluorescent proteins. Proceedings of the National Academy of Sciences of the United States of America 101(29):10554-10559. Cerca con Google

Nakai, J., M. Ohkura, and K. Imoto 2001 A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nature Biotechnology 19(2):137-141. Cerca con Google

Nguyen, N., et al. 2013 STIM1 participates in the contractile rhythmicity of HL-1 cells by moderating T-type Ca(2+) channel activity. Biochim Biophys Acta 1833(6):1294-303. Cerca con Google

Nimmrich, V., et al. 2008 Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. The Journal of Neuroscience 28(4):788-97. Cerca con Google

Oules, B., et al. 2012 Ryanodine receptor blockade reduces amyloid-b load and memory impairments in Tg2576 mouse model of Alzheimer disease. The Journal of Neuroscience 32(34):11820-34. Cerca con Google

Ozmen, L., et al. 2009 Expression of transgenic APP mRNA is the key determinant for beta-amyloid deposition in PS2APP transgenic mice. Neuro-degenerative Diseases 6(1-2):29-36. Cerca con Google

Palmer, A. E., and R. Y. Tsien 2006 Measuring calcium signaling using genetically targetable fluorescent indicators. Nature Protocols 1(3):1057-65. Cerca con Google

Parihar, M. S., and T. Hemnani 2004 Alzheimer's disease pathogenesis and therapeutic interventions. Journal of Clinical Neuroscience 11(5):456-467. Cerca con Google

Park, C. Y., A. Shcheglovitov, and R. Dolmetsch 2010 The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels. Science 330(6000):101-5. Cerca con Google

Patel, S., and R. Docampo 2010 Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. Trends in Cell Biology 20(5):277-86. Cerca con Google

Patel, S., S.K. Joseph, and A.P. Thomas 1999 Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium 25(3):247-264. Cerca con Google

Patron, M., et al. 2014 MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Molecular Cell 53(5):726-37. Cerca con Google

Paula-Lima, A. C., J. Brito-Moreira, and S. T. Ferreira 2013 Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease. Journal of Neurochemistry 126(2):191-202. Cerca con Google

Pavlov, P. F., et al. 2011 Mitochondrial g-secretase participates in the metabolism of mitochondria-associated amyloid precursor protein. Faseb Journal 25(1):78-88. Cerca con Google

Perl, D. P. 2010 Neuropathology of Alzheimer's Disease. Mount Sinai Journal of Medicine 77(1):32-42. Cerca con Google

Perrin, R. J., A. M. Fagan, and D. M. Holtzman 2009 Multimodal techniques for diagnosis and prognosis of Alzheimer's disease. Nature 461(7266):916-922. Cerca con Google

Persechini, A., J. A. Lynch, and V. A. Romoser 1997 Novel fluorescent indicator proteins for monitoring free intracellular Ca2+. Cell Calcium 22:209-216. Cerca con Google

Pierrot, N., et al. 2004 Intraneuronal amyloid-beta1-42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal death. J Neurochem 88(5):1140-50. Cerca con Google

Pietrobon, D., F. Di Virgilio, and T. Pozzan 1990 Structural and functional aspects of calcium homeostasis in eukaryotic cells. European Journal of Biochemistry 193:599-622. Cerca con Google

Pirttimaki, T. M., et al. 2013 a7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Ab effects in a preclinical Alzheimer's mouse model. PloS One 8(11):e81828. Cerca con Google

Pizzo, P., et al. 2001 Role of capacitative calcium entry on glutamate-induced calcium influx in type-I rat cortical astrocytes. Journal of Neurochemistry 79(1):98-109. Cerca con Google

Pizzo, P., et al. 2012 Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities. Pflugers Archiv : European journal of physiology 464(1):3-17. Cerca con Google

Pizzo, P., et al. 2011 Ca2+ signalling in the Golgi apparatus. Cell calcium 50(2):184-92. Cerca con Google

Podor, B., et al. 2015 Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy. Neurophotonics 2(2):021014. Cerca con Google

Pozzan, T., et al. 1994 Molecular and cellular physiology of intracellular calcium stores. Physiological Reviews 74(3):595-636. Cerca con Google

Putney, J.W., Jr., and C.M. Ribeiro 2000 Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores. Cellular and Molecular Life Sciences 57(8-9):1272-1286. Cerca con Google

Puzzo, D., et al. 2015 The Keystone of Alzheimer Pathogenesis Might Be Sought in Ab Physiology. Neuroscience 307:26-36. Cerca con Google

Raffaello, A., et al. 2013 The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J 32(17):2362-76. Cerca con Google

Rapizzi, E., et al. 2002 Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria. Journal of Cell Biology 159(4):613-624. Cerca con Google

Raychaudhury, B., et al. 2006 Peroxisome is a reservoir of intracellular calcium. Biochimica et Biophysica Acta 1760(7):989-92. Cerca con Google

Reese, L. C., and G. Taglialatela 2011 A role for calcineurin in Alzheimer's disease. Current Neuropharmacology 9(4):685-92. Cerca con Google

Resende, R., et al. 2008 Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience 155(3):725-37. Cerca con Google

Rhein, V., et al. 2009 Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proceedings of the National Academy of Sciences of the United States of America 106(47):20057-62. Cerca con Google

Richards, J. G., et al. 2003 PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. The Journal of Neuroscience 23(26):8989-9003. Cerca con Google

Rizzuto, R., et al. 1993 Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science 262(5134):744-747. Cerca con Google

Rizzuto, R., W. Carrington, and R. A. Tuft 1998 Digital imaging microscopy of living cells. Trends in Cell Biology 8:288-292. Cerca con Google

Rizzuto, R., and T. Pozzan 2006 Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiological Reviews 86(1):369-408. Cerca con Google

Rizzuto, R., et al. 1992 Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature 358(6384):325-327. Cerca con Google

Roderick, H. L., and M. D. Bootman 2003 Bi-directional signalling from the InsP3 receptor: regulation by calcium and accessory factors. Biochem Soc Trans 31(Pt 5):950-3. Cerca con Google

Rodriguez-Garcia, A., et al. 2014 GAP, an aequorin-based fluorescent indicator for imaging Ca2+ in organelles. Proc Natl Acad Sci U S A 111(7):2584-9. Cerca con Google

Ronicke, R., et al. 2011 Early neuronal dysfunction by amyloid b oligomers depends on activation of NR2B-containing NMDA receptors. Neurobiology of Aging 32(12):2219-2228. Cerca con Google

Roos, J., et al. 2005 STIM1, an essential and conserved component of store-operated Ca2+ channel function. Journal of Cell Biology 169(3):435-45. Cerca con Google

Rudolf, R., et al. 2003 Looking forward to seeing calcium. Nature Reviews. Molecular Cell Biology 4(7):579-586. Cerca con Google

Rush, T., and A. Buisson 2014 Reciprocal disruption of neuronal signaling and Abeta production mediated by extrasynaptic NMDA receptors: a downward spiral. Cell and Tissue Research 356(2):279-86. Cerca con Google

Rutter, G.A., C. Fasolato, and R. Rizzuto 1998 Calcium and organelles: a two-sided story. Biochemical and Biophysical Research Communications 253(3):549-557. Cerca con Google

Sabbioni, S., et al. 1997 GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res 57(20):4493-7. Cerca con Google

Saftig, P., and J. Klumperman 2009 Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nature Reviews. Molecular Cell Biology 10(9):623-635. Cerca con Google

Sannerud, R., et al. 2016 Restricted Location of PSEN2/gamma-Secretase Determines Substrate Specificity and Generates an Intracellular Abeta Pool. Cell 166(1):193-208. Cerca con Google

Scheenen, W. J. J. M., et al. 1998 Ca2+ depletion from granules inhibits exocytosis - A study with insulin-secreting cells. Journal of Biological Chemistry 273(30):19002-19008. Cerca con Google

Scheuner, D., et al. 1996 Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Medicine 2(8):864-70. Cerca con Google

Schreij, A. M., E. A. Fon, and P. S. McPherson 2016 Endocytic membrane trafficking and neurodegenerative disease. Cell Mol Life Sci 73(8):1529-45. Cerca con Google

Scott, H. L., et al. 2002 Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease. Journal of Neuroscience 22(3). Cerca con Google

Seidler, N. W., et al. 1989 Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem 264(30):17816-23. Cerca con Google

Selkoe, D. J., and J. Hardy 2016 The amyloid hypothesis of Alzheimer's disease at 25years. Embo Molecular Medicine 8(6):595-608. Cerca con Google

Sevigny, J., et al. 2016 Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials Experience in a Phase 1b Clinical Trial. Alzheimer Disease & Associated Disorders 30(1):1-7. Cerca con Google

Shaner, N. C., P. A. Steinbach, and R. Y. Tsien 2005 A guide to choosing fluorescent proteins. Nat Methods 2(12):905-9. Cerca con Google

Shen, J. 2014 Function and Dysfunction of Presenilin. Neurodegenerative Diseases 13(2-3):61-63. Cerca con Google

Shen, J., and J. Wu 2015 Nicotinic Cholinergic Mechanisms in Alzheimer's Disease. International Review of Neurobiology 124:275-92. Cerca con Google

Shilling, D., et al. 2012 Lack of evidence for presenilins as endoplasmic reticulum Ca2+ leak channels. The Journal of Biological Chemistry. Cerca con Google

Shilling, D., et al. 2014 Suppression of InsP3 receptor-mediated Ca2+ signaling alleviates mutant presenilin-linked familial Alzheimer's disease pathogenesis. Journal of Neuroscience 34(20):6910-23. Cerca con Google

Shim, A. H., L. Tirado-Lee, and M. Prakriya 2015 Structural and functional mechanisms of CRAC channel regulation. J Mol Biol 427(1):77-93. Cerca con Google

Shimojo, M., et al. 2007 Decreased A beta secretion by cells expressing familial Alzheimer's disease-linked mutant presenilin 1. Neuroscience Research 57(3):446-453. Cerca con Google

Shmigol, A., et al. 1994 Different properties of caffeine-sensitive Ca2+ stores in peripheral and central mammalian neurones. Pflügers Archiv 426(1-2):174-176. Cerca con Google

Shuttleworth, T. J. 2012 STIM and Orai proteins and the non-capacitative ARC channels. Front Biosci (Landmark Ed) 17:847-60. Cerca con Google

Simakova, O., and N. J. Arispe 2006 Early and late cytotoxic effects of external application of the Alzheimer's Abeta result from the initial formation and function of Abeta ion channels. Biochemistry 45(18):5907-15. Cerca con Google

Smith, I. F., et al. 2002 Ca2+ stores and capacitative Ca2+ entry in human neuroblastoma (SH- SY5Y) cells expressing a familial Alzheimer's disease presenilin-1 mutation. Brain Research 949(1-2):105-11. Cerca con Google

Sokolov, Y., et al. 2006 Soluble amyloid oligomers increase bilayer conductance by altering dielectric structure. The Journal of General Physiology 128(6):637-47. Cerca con Google

Stathopulos, P. B., and M. Ikura 2010 Partial unfolding and oligomerization of stromal interaction molecules as an initiation mechanism of store operated calcium entry. Biochem Cell Biol 88(2):175-83. Cerca con Google

Stathopulos, P. B., L. Zheng, and M. Ikura 2009 Stromal interaction molecule (STIM) 1 and STIM2 calcium sensing regions exhibit distinct unfolding and oligomerization kinetics. J Biol Chem 284(2):728-32. Cerca con Google

Stathopulos, P. B., et al. 2008 Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry. Cell 135(1):110-22. Cerca con Google

Stieren, E., et al. 2010 FAD mutations in amyloid precursor protein do not directly perturb intracellular calcium homeostasis. PLoS One 5(8):e11992. Cerca con Google

Stutzmann, G. E., et al. 2006 Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer's disease mice. The Journal of Neuroscience 26(19):5180-9. Cerca con Google

Sun, L., et al. 2015 Structural basis of human gamma-secretase assembly. Proc Natl Acad Sci U S A 112(19):6003-8. Cerca con Google

Sun, S. Y., et al. 2014 Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice. Neuron 82(1):79-93. Cerca con Google

Supnet, C., and I. Bezprozvanny 2010 Neuronal calcium signaling, mitochondrial dysfunction, and Alzheimer's disease. Journal of Alzheimer's Disease 20 Suppl 2:S487-98. Cerca con Google

- 2011 Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis. Cell Calcium 50(3):303-9. Cerca con Google

Supnet, C., et al. 2010 Up-regulation of the type 3 ryanodine receptor is neuroprotective in the TgCRND8 mouse model of Alzheimer's disease. Journal of Neurochemistry 112(2):356-65. Cerca con Google

Suzuki, J., et al. 2014 Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA. Nat Commun 5:4153. Cerca con Google

Thastrup, O., et al. 1990 Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proceedings of the National Academy of Sciences of the United States of America 87:2466-2470. Cerca con Google

Thestrup, T., et al. 2014 Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes. Nat Methods 11(2):175-82. Cerca con Google

Thibault, O., J. C. Gant, and P. W. Landfield 2007 Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store. Aging Cell 6(3):307-17. Cerca con Google

Thibault, O., R. Hadley, and P. W. Landfield 2001 Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity. Journal of Neuroscience 21(24):9744-56. Cerca con Google

Thinakaran, G., and E. H. Koo 2008 Amyloid precursor protein trafficking, processing, and function. The Journal of Biological Chemistry 283(44):29615-9. Cerca con Google

Toh, W. H., and P. A. Gleeson 2016 Dysregulation of intracellular trafficking and endosomal sorting in Alzheimer's disease: controversies and unanswered questions. Biochem J 473(14):1977-93. Cerca con Google

Tolia, A., and B. De Strooper 2009 Structure and function of gamma-secretase. Seminars in Cell & Developmental Biology 20(2):211-218. Cerca con Google

Tong, B. C., et al. 2016 Familial Alzheimer's disease-associated presenilin 1 mutants promote gamma-secretase cleavage of STIM1 to impair store-operated Ca2+ entry. Sci Signal 9(444):ra89. Cerca con Google

Tsien, R. Y. 1980 New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry 19(11):2396-404. Cerca con Google

- 1998 The green fluorescent protein. Annual Review of Biochemistry 67:509-544. Cerca con Google

Tsien, R. Y., T. Pozzan, and T. J. Rink 1982 Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. Journal of Cell Biology 94:325-334. Cerca con Google

Tsien, R. Y., and D. Prasher 1998 Molecular biology and mutation of GFP. Methods in Cell Biology in press. Cerca con Google

Tu, H., et al. 2006 Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell 126(5):981-93. Cerca con Google

Um, J. W., et al. 2013a Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer ab oligomer bound to cellular prion protein. Neuron 79(5):887-902. Cerca con Google

- 2013b Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 79(5):887-902. Cerca con Google

Um, J. W., et al. 2012 Alzheimer amyloid-beta oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nature neuroscience 15(9):1227-35. Cerca con Google

Vais, H., et al. 2016 EMRE Is a Matrix Ca(2+) Sensor that Governs Gatekeeping of the Mitochondrial Ca(2+) Uniporter. Cell Rep 14(3):403-10. Cerca con Google

Veng, L. M., M. H. Mesches, and M. D. Browning 2003 Age-related working memory impairment is correlated with increases in the L-type calcium channel protein a1D (Cav1.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Brain Research. Molecular Brain Research 110(2):193-202. Cerca con Google

Verkhratsky, A., et al. 2016 Astroglia dynamics in ageing and Alzheimer's disease. Current Opinion in Pharmacology 26:74-79. Cerca con Google

Vig, M., et al. 2006 CRACM1 multimers form the ion-selective pore of the CRAC channel. Current Biology 16(20):2073-9. Cerca con Google

Villasenor, R., Y. Kalaidzidis, and M. Zerial 2016 Signal processing by the endosomal system. Curr Opin Cell Biol 39:53-60. Cerca con Google

Walker, E. S., et al. 2005 Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. Journal of Neurochemistry 92(2):294-301. Cerca con Google

Walsh, D. M., et al. 2002a Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535-9. Cerca con Google

Walsh, D. M., et al. 2002b Amyloid-b oligomers: their production, toxicity and therapeutic inhibition. Biochemical Society Transactions 30(4):552-557. Cerca con Google

Wandinger-Ness, A., and M. Zerial 2014 Rab proteins and the compartmentalization of the endosomal system. Cold Spring Harb Perspect Biol 6(11):a022616. Cerca con Google

Wang, H. Y., et al. 2000 b-Amyloid1-42 binds to a7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology. The Journal of Biological Chemistry 275(8):5626-32. Cerca con Google

Wang, Y., X. Deng, and D. L. Gill 2010a Calcium signaling by STIM and Orai: intimate coupling details revealed. Science Signaling 3(148):pe42. Cerca con Google

Wang, Y., et al. 2010b The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels. Science 330(6000):105-9. Cerca con Google

Williams, R. T., et al. 2001 Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins. Biochem J 357(Pt 3):673-85. Cerca con Google

Wissenbach, U., et al. 2007 Primary structure, chromosomal localization and expression in immune cells of the murine ORAI and STIM genes. Cell Calcium 42(4-5):439-46. Cerca con Google

Wojda, U., E. Salinska, and J. Kuznicki 2008 Calcium ions in neuronal degeneration. IUBMB Life 60(9):575-90. Cerca con Google

Wolfe, M. S. 2007 When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. EMBO Report 8(2):136-40. Cerca con Google

Wong, A. K., et al. 2013 Heterogeneity of Ca2+ handling among and within Golgi compartments. J Mol Cell Biol 5(4):266-76. Cerca con Google

Wu, J., et al. 2016 Heteromeric alpha7beta2 Nicotinic Acetylcholine Receptors in the Brain. Trends in pharmacological sciences 37(7):562-74. Cerca con Google

Wuytack, F., L. Raeymaekers, and L. Missiaen 2002 Molecular physiology of the SERCA and SPCA pumps. Cell Calcium 32(5-6):279-305. Cerca con Google

Yoo, A.S., et al. 2000 Presenilin-mediated modulation of capacitative calcium entry. Neuron 27(3):561-572. Cerca con Google

You, H. T., et al. 2012 Ab neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. Proceedings of the National Academy of Sciences of the United States of America 109(5):1737-1742. Cerca con Google

Zahs, K. R., and K. H. Ashe 2010 'Too much good news' - are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer's disease? Trends Neurosci 33(8):381-9. Cerca con Google

Zalk, R., et al. 2015 Structure of a mammalian ryanodine receptor. Nature 517(7532):44-9. Cerca con Google

Zampese, E., et al. 2009 Ca2+ dysregulation mediated by presenilins in Familial Alzheimer'™s Disease: causing or modulating factor? Current Trends in Neurology 3:1-14. Cerca con Google

Zampese, E., et al. 2011a Presenilin-2 modulation of ER-mitochondria interactions. Communicative & Integrative Biology 4(3):357-360. Cerca con Google

Zampese, E., et al. 2011b Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proceedings of the National Academy of Sciences of the United States of America 108(7):2777-82. Cerca con Google

Zampese, E., and P. Pizzo 2012 Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes? Cellular and molecular life sciences : CMLS 69(7):1077-104. Cerca con Google

Zatti, G., et al. 2006 Presenilin mutations linked to familial Alzheimer's disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium 39(6):539-50. Cerca con Google

Zatti, G., et al. 2004 The presenilin 2 M239I mutation associated with familial Alzheimer's disease reduces Ca2+ release from intracellular stores. Neurobiology of Disease 15(2):269-278. Cerca con Google

Zeiger, W., et al. 2013 Ca2+ Influx through Store-operated Ca2+ Channels Reduces Alzheimer Disease b-Amyloid Peptide Secretion. Journal of Biological Chemistry 288(37):26955-26966. Cerca con Google

Zempel, H., et al. 2010 Ab oligomers cause localized Ca2+ elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. The Journal of Neuroscience 30(36):11938-50. Cerca con Google

Zhang, H., et al. 2016 Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment. J Neurosci 36(47):11837-11850. Cerca con Google

Zhang, H., et al. 2015a Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease. Journal of Neuroscience 35(39):13275-86. Cerca con Google

Zhang, S. L., et al. 2006 Genome-wide RNAi screen of Ca2+ influx identifies genes that regulate Ca2+ release-activated Ca2+ channel activity. Proceedings of the National Academy of Sciences of the United States of America 103(24):9357-62. Cerca con Google

Zhang, X., C. J. Yu, and S. S. Sisodia 2015b The topology of pen-2, a gamma-secretase subunit, revisited: evidence for a reentrant loop and a single pass transmembrane domain. Mol Neurodegener 10:39. Cerca con Google

Zheng, H., and E. H. Koo 2006 The amyloid precursor protein: beyond amyloid. Molecular Neurodegeneration 1. Cerca con Google

Zheng, L., et al. 2008 Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2. Biochem Biophys Res Commun 369(1):240-6. Cerca con Google

Zhou, Y., et al. 2010 STIM1 gates the store-operated calcium channel ORAI1 in vitro. Nat Struct Mol Biol 17(1):112-6. Cerca con Google

Zhou, Y., et al. 2013 Initial activation of STIM1, the regulator of store-operated calcium entry. Nat Struct Mol Biol 20(8):973-81. Cerca con Google

Zhu, M. X., et al. 2010a Calcium signaling via two-pore channels: local or global, that is the question. American Journal of Physiology. Cell Physiology 298(3):C430-41. Cerca con Google

Zhu, M. X., et al. 2010b TPCs: Endolysosomal channels for Ca2+ mobilization from acidic organelles triggered by NAADP. FEBS Letters 584(10):1966-74. Cerca con Google

Zitt, C., et al. 2004 Potent inhibition of Ca2+ release-activated Ca2+ channels and T-lymphocyte activation by the pyrazole derivative BTP2. J Biol Chem 279(13):12427-37. Cerca con Google

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