Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Florean, Cristina (2009) Messa a punto di un nuovo metodo biomolecolare per la misura dell’attività gamma-secretasica in cellule viventi. [Ph.D. thesis]

Full text disponibile come:

[img]Documento PDF
Thesis not accessible for intellectual property related reasons.
Visibile to: nobody
2552Kb

Abstract (english)

gamma-Secretase mediates the intramembranous proteolysis of amyloid precursor protein (APP), Notch and other cellular substrates and is considered a prime pharmacological target in the development of therapeutics for Alzheimer's disease (AD) and cancer. We describe here an efficient, new, simple, sensitive and rapid assay to quantify gamma-secretase activity in living cells by flow cytometry using membrane-bound fluorescent probes, APP-GFP or C99-GFP,and Notch-De GFP as substrates for gamma-secretase. By applying two well-known gamma-secretase inhibitors (DAPT and L-685,458), we validated our assay showing that the positional GFP-based probes for gamma-secretase activity behave properly when expressed in different cell lines. Moreover, by co-expression of different familial AD-linked mutated forms of presenilin--the key component of the gamma-secretase complex--in cells devoid of any endogenous gamma-secretase, our method allowed us to evaluate in situ the contribution of different presenilin variants to the modulation of the enzyme.

Abstract (italian)

La gamma secretasi media la proteolisi in un sito intramembrana della proteina precursore dell'amiloide (APP), di Notch e di altri substrati cellulari, ed è considerata un target farmacologico primario nella ricerca per la terapia della malattia di Alzheimer e recentemente per il cancro. In questo lavoro è descritto un nuovo, semplice e rapido test per misurare l'attività di questo enzima in cellule viventi usando delle sonde fluorescenti membranose, APP-GFP, C99-GFP e NotchDeGFP, come substrati della gamma secretasi. Abbiamo convalidato il test applicando degli inibitori dell'enzima noti (DAPT and L-685,458), mostrando che le nostre sonde posizionali funzionano bene espresse in diverse linee cellulari. Inoltre, coesprimendo diverse forme doi presenilina (il centro catalitico della secretasi) è stato valutato il ruolo delle varianti di presenilina nella modulazione dell'enzima.

Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Pizzo, Paola and De Giorgi, Francesca
Ph.D. course:Ciclo 21 > Scuole per il 21simo ciclo > BIOSCIENZE > NEUROBIOLOGIA
Data di deposito della tesi:28 January 2009
Anno di Pubblicazione:2009
Key Words:Alzheimer, gamma secretasi, Presenilina, APP, Notch, citometria di flusso.
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/15 Biologia farmaceutica
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Biomediche Sperimentali
Codice ID:1563
Depositato il:28 Jan 2009
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
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.

Aleksic T, Feller SM. “Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells.” Cell Commun Signal. 2008 Oct 24;6:8. Cerca con Google

Allinson TM, Parkin ET, Turner AJ, Hooper NM. “ADAMs family members as amyloid precursor protein alpha-secretases” J Neurosci Res. 2003 Nov 1;74(3):342-52. Cerca con Google

Araki W, Takahashi-Sasaki N, Chui DH, Saito S, Takeda K, Shirotani K, Takahashi K, Murayama KS, Kametani F, Shiraishi H, Komano H, and Tabira T. “A family of membrane proteins associated with presenilin expression and ?-secretase function” The FASEB Journal fj.07-9072, 2007. Cerca con Google

Baki L, Neve RL, Shao Z, Shioi J, Georgakopoulos A, Robakis NK. “Wild-type but not FAD mutant presenilin-1 prevents neuronal degeneration by promoting phosphatidylinositol 3-kinase neuroprotective signaling.” J Neurosci 2008;28:483-90. Cerca con Google

Banwait S, Galvan V, Zhang J, Gorostiza OF, Ataie M, Huang W, Crippen D, Koo EH, Bredesen DE “C-terminal cleavage of the amyloid-beta protein precursor at Asp664: a switch associated with Alzheimer's disease.” J Alzheimers Dis. 2008 Feb;13(1):1-16. Cerca con Google

Beel AJ, Sanders CR “Substrate specificity of gamma-secretase and other intramembrane proteases.” Cell Mol Life Sci. 2008 May;65(9):1311-34 Cerca con Google

Beglopoulos V, Sun X., Saura CA, Lemere C, Kim RD, Shen J. “Reduced ?-amyloid production and increased inflammatory responses in presenilin conditional knocked out mice.” JBC, Vol 279, N.45, Issue of November 5, pp 46907-46914, 2004. Cerca con Google

Berechid BE, Kitzmann M, Foltz DR, Roach AH, Seiffert D, Thompson LA, Olson RE, Bernstein A, Donoviel DB, Nye JS, “Identification and characterization of presenilin-independent Notch signalling”. J. Biol. Chem. 277 (2002) 8154–8165. Cerca con Google

Berezovska O, Jack Christine, McLean P, Aster J, Hicks C, Xia W, Wolfe MS, Kimberly WT, Weinmaster G, Selkoe DJ, Hyman BT. “Aspartate Mutations in Presenilin and ?-secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch1 signaling.” J Neurochem. 75, 583-593 (2000) Cerca con Google

Bernstein HG, Bukowska A, Krell D, Bogerts B, Ansorge S,Lendeckel U. ”Comparative localization of ADAMs 10 and 15 in human cerebral cortex normal aging, Alzheimer disease and Down syndrome.” J Neurocytol. 2003 Feb;32(2):153-60. Cerca con Google

Brunello L, Zampese E, Florean C, Pozzan T, Pizzo P and Fasolato C .“Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake.” J Cell Mol Med., submitted paper. Cerca con Google

Cheung KH, Shineman D, Müller M, Cárdenas C, Mei L, Yang J, Tomita T, Iwatsubo T, Lee VM, Foskett JK “Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating.” Neuron. 2008 Jun 26;58(6):871-83 Cerca con Google

Clarke EE, “Intra or inter complex binding to the ?-secretase enzyme: a model to differentiate inhibitor classes. “ J Biol Chem. 2006 Oct 20;281(42):31279-89. Cerca con Google

Costa RM, Drew C, Silva AJ. “Notch to remember” Trends Neurosci. 2005 Aug;28(8):429-35 Cerca con Google

Czirr E, Weggen S ”?-Secretase Modulation with A?42-Lowering Nonsteroidal Anti-Inflammatory Drugs and Derived Compounds” Neurodegenerative Dis 2006;3:298–304 Cerca con Google

De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature; 398(6727); 518-22 (1999). Cerca con Google

De Strooper B, “Loss of function presenilin mutations in Alzheimer disease. Talking point in the role of Presenilin mutations in Alzheimer disease, EMBO Rep 8 (2007) 141-146. Cerca con Google

Doedens JR, Black R, “Stimulation-induced down-regulation of Tumor Necrosis Factor-? converting Enzyme” JBC, Vol 275, N.19, Issue of May, pp.14598-14607, 2000. Cerca con Google

Dolcini V, Dunys J, Sevalle J, Chen F, Guillot-Sestier MV, StGeorge-Hyslop P, Fraser PE, Checler F. “TMP21 regulates A? production but does not affect caspase-3, p53, and neprilysin.” Biochem Biophys Res Commun.2008 Jun 20;371(1):69-74. Cerca con Google

Dovey HF, John V, Anderson JP, Chen LZ, De Saint Andrieu P, Fang LY, SB, Freedman, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson-Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, R.N. Motter, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel L.D., Bende MHr, Boggs LN, Britton TCClemens JC, Czilli DL, Dieckman-McGinty DK Droste JJ, Fuson KS, Gitter BD, HyslopPA, Johnstone EM, Li WY, Little SP,.Mabry TE, Morohashi Y, Kan T, Tominari Y, Fuwa H, Okamura Y, Watanabe N, Sato C, Natsugari H, Fukuyama T, Iwatsubo T, Tomita T, “C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester)”, J. Biol. Chem. 281 (2006) 14670–14676. Cerca con Google

Edbauer D, Willem M, Lammich S, Steiner H, and Haass C. “Insulin-degrading Enzyme Rapidly Removes the ?-Amyloid Precursor Protein Intracellular Domain (AICD)”. JBC, Vol. 277, No. 16, pp. 13389–13393, 2002 Cerca con Google

Flajolet M, He G, Heiman M, Lin A, Nairn AC, and Greengard P. “Regulation of Alzheimer's disease amyloid-beta formation by casein kinase I” PNAS, 2007;104;4159-4164; Cerca con Google

Florean C, Zampese E, Zanese M , Brunello L, Ichas F, De Giorgi F, Pizzo P “High content analysis of ?-secretase activity reveals variable dominance of presenilin mutations linked to familial Alzheimer's disease” Biochim. Biophys. Acta (2008), doi:10.1016/j. bbamcr. 2008.03.012 Cerca con Google

Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, LeBlanc A, Smith D, Rigby M, Shearman MS, Clarke EE, Zheng H, Van Der Ploeg LH, Ruffolo SC, Thornberry NA, Xanthoudakis S, Zamboni RJ, Roy S, Nicholson DW, “ Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A??peptide formation”, Cell 97 (1999) 395–406. Cerca con Google

Giliberto L, Zhou D, Weldon R, Tamagno E, De Luca P, Tabaton M and D'Adamio L “Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role.” Molecular Neurodegeneration 2008, 3:12 doi:10.1186/1750-1326-3-12 Cerca con Google

Gonzales PE, Galli JD, Milla ME, “Identification of key sequence determinants for the inhibitory function of the prodomain of TACE”. Biochemistry 2008, 9911-9919 Cerca con Google

Green K, LaFerla F “Linking Calcium to A? and Alzheimer's Disease” Neuron, Volume 59, Issue 2, Pages 190 - 194 Cerca con Google

Ha Y “Structural principles of intramembrane proteases.” Curr Opin Struct Biol. 2007 Aug;17(4):405-11. Cerca con Google

Hansson CA, Frykman S, Farmery MR, Tjenberg LO, Nilsberth C, Pursgloves SE, Ito A, Winblad B, Cowburn RF, Thyberg J, Ankarcrona M. “Nicastrin, Presenilin, APH-1 and PEN-2 form active ?-secretase complexes in mitochondria.” JBC, Vol.279, N.49, Issue of December 3, pp 51654-51660 (2004) Cerca con Google

Hass M R, Sato C, Kopan R, Zhao G. “Presenilin: Rip and Beyond.” Semin Cell Dev Biol. 2008 Nov 27. Cerca con Google

Hemming ML, Elias JE, Gygi SP, Selkoe DJ “Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements.” PLoS Biol. 2008 Oct 21;6(10):e257. Cerca con Google

Hoke DE, Tan JL, Ilaya NT, Culvenor JG, Smith SJ, White AR, Masters CL and. Evin GM. “In vitro gamma-secretase cleavage of the Alzheimer’s amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc” FEBS Journal 272 (2005) 5544–5557 Cerca con Google

Hwang EM, Kim SK, Sohn JH, Lee JY, Kim Y, Kim YS, Jung IM.”Furin is an endogenous regulator of ?-secretase associated APP processing”. BBRC 349 (2006) 654-659. Cerca con Google

Ichas F, De Giorni F, Piazza PV, Dessolin J, Schembri L, Tomasello F, Lartigue L, “Method for demonstration of a molecular event in a cell by means of fluorescent markers protein [French Patent No FR2857098 and World Patent Filing No WO2005/012913], (2005). Cerca con Google

Irvine GB, El-Agnaf OM, Shankar GM, and Walsh DM “Protein Aggregation in the Brain: The Molecular Basis for Alzheimer’s and Parkinson’s Diseases” Mol Med. 2008 Jul–Aug; 14(7-8): 451–464 Cerca con Google

Joa DG, Janga J, Kima BJ, Lundkvistb J, Junga YK. “Overexpression of calsenilin enhances ?-secretase activity” Neuroscience Letters 378 (2005) 59–64. Cerca con Google

Kaether C, Schmitt S, Willem M, Haass C “Amyloid precursor protein and Notch intracellular domains are generated after transport of their precursors to the cell surface.” Traffic. 2006 Apr;7(4):408-15. Cerca con Google

Kakuda N, Funamoto S, Yagishita S, Takami M, Osawa S, Dohmae N, and Ihara Y. “Equimolar Production of Amyloid ?-Protein and Amyloid Precursor Protein Intracellular Domain from ?-Carboxyl-terminal Fragment by ?-Secretase”. JBC VOL. 281, NO. 21, pp. 14776–14786, May 26, 2006 Cerca con Google

Kim ML, Zhang B, Mills IP, Milla ME, Brunden KR, Lee VM. “Effects of TNF alpha-converting enzyme inhibition on amyloid beta production and APP processing in vitro and in vivo.” J Neurosci. 2008 Nov 12;28(46):12052-61. Cerca con Google

Kim SK, Park HJ, Hong HS, Baik EJ, Jung MW, Jung IM, “ERK1/2 is an endogenous negative regulator of the ?-secretase activity” The FASEB Journal express article 10.1096/fj.05-4055fje. November 17, 2005. Cerca con Google

Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ. “The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a Notch-like manner.” J Biol Chem 276 (43): 40288-92 (2001). Cerca con Google

Knops J, Suomensaari S, Lee M, McConlogue L, Seubert P, Sinha S. “Cell-type and amyloid precursor protein-type specific inhibition of A beta release by bafilomycin A1, a selective inhibitor of vacuolar ATPases.”J Biol Chem. 1995 Feb 10;270(6):2419-22. Cerca con Google

Kornilova AY, Das D, Wolfe MS. “Differential effects of inhibitors on the ?-secretase complex. JBC Vol. 278 N.19, Issue of May 9, pp 16470-16473, 2003. Cerca con Google

Lai MT, Chen E, Crouthamel MC, DiMuzio-Mower J, Xu M, Huang Q, Price E, Register RB, Shi XP, Donoviel DB, Bernstein A, Hazuda D, Gardell SJ, Li YM, ”Presenilin-1 and presenilin-2 exhibit distinct yet overlapping ?-secretase activities” J. Biol. Chem. 278 (2003) 22475–22481. Cerca con Google

La Ferla FM “Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease.” Nat Rev Neurosci 3, 862-872 (2002). Cerca con Google

Laudon H, Karlstrom H, Mathews PM, Farmery MR, Gandy SE, Lundkvist J, Lendahl U, Naslund J. “Functional domains in Presenilin 1” JBC, Vol.279, N.23, Issue of June, 23925-23932, 2004. Cerca con Google

Lazarov VK, Fraering PC, Ye W, Wolfe MS, Selkoe DJ and Li H. “Electron microscopic structure of purified, active ?-secretase reveals an aqueous intramembrane chamber and two pores.” PNAS, vol.103 n.18, 6889-6894, May 2, 2006. Cerca con Google

Leissring M.A, Murphy MP, Mead TR, Akbari Y, Sugarman MC, Jannatipour M, Anliker B, Muller U, Saftig P, De Strooper B, Wolfe MS, Golde TE, and La Ferla FM. “A physiological signaling role for the ?-secretase derived intracellular fragment of APP”, PNAS vol.99 no.7,4697-4702, 2002. Cerca con Google

Liao YF, Wang BJ, Cheng HT, Kuo LH, and Wolfe MS, “Tumor Necrosis Factor-?, Interleukin-1?, and Interferon-? Stimulate ?-Secretase-mediated Cleavage of Amyloid Precursor Protein through a JNK-dependent MAPK Pathway” J Biol Chem. 2004 Nov 19;279(47):49523-32 Cerca con Google

Ma QH, Futagawa T, Yang WL, Jiang XD, Zeng L, Takeda Y, Xu RX, Bagnard D, Schachner M, Furley AJ, Karagogeos D, Watanabe K, Dawe GS, Xiao ZC. “A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.” Nat Cell Biol. 2008 Mar;10(3):283-94. Epub 2008 Feb 17. Cerca con Google

Miyake K e Nagai K. “Inhibition of ?-mannosidase attenuates endoplasmic reticulum stress-induced neuronal cell death”, NeuroToxicology 6 November 2008 Cerca con Google

Morohashi Y, Kan T, Tominari Y, Fuwa H, Okamura Y, Watanabe N, Sato C, Natsugari H, Fukuyama T, Iwatsubo T, Tomita T. “C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma-secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester).” J Biol Chem. 2006 May 26;281(21):14670-6. Cerca con Google

Miller FD, Audia JE, “Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain”, J. Neurochem. 76 (2001) 173–181. Cerca con Google

Müller T, Meyer HE, Egensperger R, Marcus K.The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog Neurobiol. 2008 Aug;85(4):393-406. Cerca con Google

Petit A, Bihel F, Alves da Costa C, Pourquié O, Checler F and Kraus JL. “New protease inhibitors prevent ?-secretase-mediated production of A?40/42 without affecting Notch cleavage.” Nature Cell Biology, Vol.3, May 2001, 507-511. Cerca con Google

Pinnix I, Musunuru U, Tun H, Sridharan A, Golde T, Eckman C, Ziani-Cherif C, Onstead L, and Sambamurti K “A Novel ?-Secretase Assay Based on Detection of the Putative C-terminal Fragment of Amyloid ??Protein Precursor” JBC Vol. 276, No. 1, Issue of January 5, pp. 481–487, 2001 Cerca con Google

Rizzo P, Osipo C, Foreman K, Golde T, Osborne B, Miele L. “Rational targeting of Notch signalling in cancer.” Oncogene, (2008) 27, 5124-5131. Cerca con Google

Sernee MF, Evin G, Culvenor JG, Villadangos JA, Beyreuther K, Masters CL and Cappai R. “Selecting cells with different Alzheimer’s disease ?-secretase activity using FACS. Differential effect of presenilin exon 9 deletion on ?- and ?-cleavage” Eur. J. Biochem. 270, 495–506 (2003). Cerca con Google

Shearman MS, Beher D, Clarke EE, Lewis HD, Harrison T, Hunt P, Nadin A, Smith AL, Stevenson G and Castro JL. “L-685, 458, an aspartil protease transition state mimic, is a potent inhibitor of amyloid-? protein precursor ?-secretase activity.” Biochemistry 2000, 39, 8698-8704. Cerca con Google

Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S, “Skeletal and CNS defects in Presenilin-1 deficient mice.”Cell 89 (1997) 629-639 Cerca con Google

Shen J, Kelleher RJ 3rd. “The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism.” Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):403-9. Cerca con Google

Tamagno E, Guglielmotto M, Aragno M, Borghi R, Autelli R, Giliberto L, Muraca G, Danni O, Zhu X, Smith MA, Perry G, Jo DG, Mattson MP, Tabaton M.“Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein.” J Neurochem. 2008 Feb;104(3):683-95. Cerca con Google

Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH, Serneels L, De Strooper B, Yu G, Bezprozvanny I. “Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations.” Cell. 2006 Sep 8;126(5):981-93. Cerca con Google

Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G & Citron M.?“?-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.” Science 286, 735-741, 1999 Cerca con Google

Venezia V, Nizzari M, Carlo P, Corsaro A, Floria T, Russo C, “Amyloid Precursor Protein and Presenilin Involvement in Cell Signaling” Neurodegenerative Dis 2007;4:101–111DOI: 10.1159/000101834 Cerca con Google

Verdile G, Gandy SE, Martins RN. ”The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid.” Neurochem Res. 2007 Apr-May;32(4-5):609-23. Cerca con Google

Wolfe MS, Guénette SY, “APP at a glance”. J Cell Sci. 2007 Sep 15;120(Pt 18):3157-61. Cerca con Google

Wolfe MS. “Gamma-secretase inhibition and modulation for Alzheimer's disease.” Curr Alzheimer Res. 2008 Apr;5(2):158-64. Cerca con Google

Wolfe MS, “The gamma-secretase complex: membrane-embedded proteolytic ensemble.” Biochemistry. 2006 Jul 4;45(26):7931-9 Cerca con Google

Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashler JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME, “Membrane-anchored aspartyl protease with Alzheimr’s disease ?-secretase activity” Nature 402, 533-537, 1999. Cerca con Google

Yoshiike Y. “Specific compositions of amyloid-? peptides as the determinant of toxic ?-aggregation.” The Journal of Biological Chemistry, vol 278, No 26, 23648-23655 (2003). Cerca con Google

Yu G, Chen F, Nishimura M, Steiner H, Tandon A, Kawarai T, Arawaka S, Supala A, Song YQ, Rogaeva E, Holmes E, Zhang DM, Milman P, Fraser P, Haass C and St.George-Hyslop P. “Mutation of conserved aspartates affects maturation of both aspartate mutant and endogenous Presenilin 1 and Presenilin 2 complexes”. JBC, Vol 275, n. 35, pp 27348-27353, (2000). Cerca con Google

Zatti G, Burgo A, Giacomello M, Barbiero L, Guidoni R, Sinigaglia G, Florean C, Bagnoli S, Binetti G, Sorbi S, Pizzo P, Fasolato C, “Presenilin mutations linked to familial Alzheimer's disease reduce endoplasmic reticulum and Golgi apparatus calcium levels”, Cell Calcium 39 (2006) 539–550. Cerca con Google

Zhang C, Khandelwal PJ, Chakraborty R, Cuellar TL, Sarangi S, Patel SA, Cosentino CP, O'Connor M, Lee JC, Tanzi RE, Saunders AJ, “An AICD-based functional screen to identify APP metabolism regulators”, Mol Neurodegener 2 (2007) 15. Cerca con Google

Zhang M, Haapasalo A, Kim DY, MacKenzie Ingano LA, Pettingell WH, and Kovacs DM, “Presenilin/?-secretase activity regulates protein clearance from the endocytic recycling compartment.” The FASEB Journal, FJ Express Summary 3Vol. 20, June 2006 Cerca con Google

Zhou S, Zhou H, Walian PJ, and Bing K. “CD147 is a regulatory subunit of the ?-secretase complex in Alzheimer’s disease amyloid ?-peptide production”, Biochemistry. 2007 Mar 13;46(10):2553-63 Cerca con Google

Ziani-Cherif C, Mostefa-Kara B and Brixi-Gormat FZ. “Gamma-Secretase as a Pharmacological Target in Alzheimer Disease. When, Why and How?” Current Pharmaceutical Design, 2006, 12, 4313-4335 4313 1381-6128/06 Cerca con Google

Solo per lo Staff dell Archivio: Modifica questo record

EPrints Logo
Padua@Research is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.