Scientific article

Prevention of apoptotic neuronal death by controlling procaspases? A point of view

Published inBrain research reviews, vol. 36, no. 2-3, p. 196-203
Publication date2001

In various animal models of neurodegenerative diseases the long-lasting control of cell death by anti-apoptotic therapies is not successful. We present here our view on the control of procaspase expression in a model of cerebral stroke. We have investigated how Hu-Bcl-2 overexpression modifies cell death protein activation in a model of cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO). In wild type mice MCAO induced release of cytochrome c from the mitochondria, and activation of caspases 9 and 3. In parallel with caspases activation, procaspase 9 and procaspase 3 were, respectively, increased and decreased. In Hu-Bcl-2 transgenic mice cytochrome c release and caspases 9 and 3 activation were blocked. However procaspase 9 increased, like in wt mice, but procaspase 3 remained unchanged. By 2 weeks after MCAO caspases were no longer blocked in Hu-Bcl-2 transgenic mice. Procaspase 9 increase could represent a time bomb in Hu-Bcl-2 mice where caspase 9 activation is blocked. Indeed, cellular accumulation of procaspase 9 is a potentially harmful event able to overcome anti-apoptotic protection by Bcl-2 and threaten cells with rapid destruction. Through understanding of the upstream regulation of procaspase 9, early targets for the pharmacological control of apoptotic cell death may be revealed.

  • Animals
  • Apoptosis/physiology
  • Brain Ischemia/drug therapy/enzymology/physiopathology
  • Caspase 9
  • Caspases/metabolism
  • Enzyme Precursors/metabolism
  • Gene Expression Regulation, Enzymologic/physiology
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases/drug therapy/enzymology/physiopathology
  • Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
Citation (ISO format)
DUBOIS-DAUPHIN, Michel et al. Prevention of apoptotic neuronal death by controlling procaspases? A point of view. In: Brain research reviews, 2001, vol. 36, n° 2-3, p. 196–203. doi: 10.1016/s0165-0173(01)00095-9
Main files (1)
Article (Published version)
ISSN of the journal0165-0173

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