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Bcl2-A1 interacts with pro-caspase-3: implications for amyotrophic lateral sclerosis

Iaccarino, Ciro and Mura, Maria Elena and Esposito, Sonia and Carta, Franco and Sanna, Giovanna and Turrini, Francesco Michelangelo and Carrì, Maria Teresa and Crosio, Claudia (2011) Bcl2-A1 interacts with pro-caspase-3: implications for amyotrophic lateral sclerosis. Neurobiology of Disease, Vol. 43 (3), p. 642-650. ISSN 0969-9961. Article.

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DOI: 10.1016/j.nbd.2011.05.013

Abstract

Expression of mutant SOD1 typical of familial amyotrophic lateral sclerosis (ALS) induces the expression of Bcl2-A1, a member of the Bcl2 family of proteins, specifically in motor neurons of transgenic mice.
In this work, we have used immortalized motor neurons (NSC-34) and transgenic mice expressing mutant SOD1 to unravel the molecular mechanisms and the biological meaning of this up-regulation. We report that up-regulation of Bcl2-A1 by mutant SOD1 is mediated by activation of the redox sensitive transcription factor AP1 and that Bcl2-A1 interacts with pro-caspase-3 via its C-terminal helixα9. Furthermore, Bcl2-A1 inhibits pro-caspase-3 activation in immortalized motor neurons expressing mutant SOD1 and thus induction of Bcl2-A1 in ALS mice represents a pro-survival strategy aimed at counteracting the toxic effects of mutant SOD1.
These data provide significant new insights on how molecular signaling, driven by expression of the ALS-causative gene SOD1, affects regulation of apoptosis in motor neurons and thus may have implications for ALS therapy, where prevention of motor neuronal cell death is one of the major aims.

Item Type:Article
ID Code:6228
Status:Published
Refereed:Yes
Uncontrolled Keywords:ALS, amyotrophic lateral sclerosis, apoptosis, pro-caspase-3, Bcl2-A1, mutant SOD1, NSC34 cells
Subjects:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Nurex Bioresearch Sassari, Sassari
001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
Publisher:Academic Press / Elsevier
ISSN:0969-9961
Copyright Holders:© 2011 Elsevier
Deposited On:07 Jul 2011 12:01

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