Bcl2-A1 interacts with pro-caspase-3

Implications for amyotrophic lateral sclerosis

Ciro Iaccarino, Maria Elena Mura, Sonia Esposito, Franco Carta, Giovanna Sanna, Franco Turrini, Maria Teresa Carrì, Claudia Crosio

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 helix α9. 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.

Original languageEnglish
Pages (from-to)642-650
Number of pages9
JournalNeurobiology of Disease
Volume43
Issue number3
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
Caspase 3
Transgenic Mice
Up-Regulation
Poisons
Oxidation-Reduction
Cell Death
Transcription Factors
Apoptosis
Genes
Proteins
Therapeutics

Keywords

  • ALS
  • Apoptosis
  • Bcl2-A1
  • Mutant SOD1
  • NSC34 cells
  • Pro-caspase-3

ASJC Scopus subject areas

  • Neurology

Cite this

Iaccarino, C., Mura, M. E., Esposito, S., Carta, F., Sanna, G., Turrini, F., ... Crosio, C. (2011). Bcl2-A1 interacts with pro-caspase-3: Implications for amyotrophic lateral sclerosis. Neurobiology of Disease, 43(3), 642-650. https://doi.org/10.1016/j.nbd.2011.05.013

Bcl2-A1 interacts with pro-caspase-3 : Implications for amyotrophic lateral sclerosis. / Iaccarino, Ciro; Mura, Maria Elena; Esposito, Sonia; Carta, Franco; Sanna, Giovanna; Turrini, Franco; Carrì, Maria Teresa; Crosio, Claudia.

In: Neurobiology of Disease, Vol. 43, No. 3, 09.2011, p. 642-650.

Research output: Contribution to journalArticle

Iaccarino, C, Mura, ME, Esposito, S, Carta, F, Sanna, G, Turrini, F, Carrì, MT & Crosio, C 2011, 'Bcl2-A1 interacts with pro-caspase-3: Implications for amyotrophic lateral sclerosis', Neurobiology of Disease, vol. 43, no. 3, pp. 642-650. https://doi.org/10.1016/j.nbd.2011.05.013
Iaccarino, Ciro ; Mura, Maria Elena ; Esposito, Sonia ; Carta, Franco ; Sanna, Giovanna ; Turrini, Franco ; Carrì, Maria Teresa ; Crosio, Claudia. / Bcl2-A1 interacts with pro-caspase-3 : Implications for amyotrophic lateral sclerosis. In: Neurobiology of Disease. 2011 ; Vol. 43, No. 3. pp. 642-650.
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