Role of mitochondrial proteins for neuronal cell death after focal cerebral ischemia.
Cell death following focal cerebral ischemia has an acute and a delayed component. Delayed neuronal cell death occurs via activation of molecular signalling pathways resembling apoptosis in nonneuronal cells. Cell surface cell death receptors and damage to mitochondria or DNA initiate these pathways finally leading to DNA fragmentation and cell death. Central mediators of delayed neuronal cell death are two families of molecules: a group of cysteine aspartate proteases, called caspases, and molecules of the bcl-2 family, e.g. bcl-2, bax, and bid. Caspases initiate and execute cell death, while bcl-2 family members modulate death signalling and lead to release of pro-apoptotic molecules from the mitochondrial intermembranous space, e.g. cytochrome c and apoptosis inducing factor (AIF). Cytochrome c induces cell death by activation of caspase 9 and 3, while AIF leads to detrimental DNA damage by an capase-independent pathway. The current paper reviews recent findings dealing with pre- and post-mitochondrial cell death pathways activated by focal cerebral ischemia.
Plesnila
N
N
Institute for Surgical Research, University of Munich, Munich, Germany. plesnila@icf.med.uni-muenchen.de
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D005420:Flavoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases