Apoptosis: a target for neuroprotection.
Accumulating evidence strongly suggests that apoptosis contributes to neuronal death in a variety of neurodegenerative contexts. Activation of the cysteine protease caspase 3 appears to be a key event in the execution of apoptosis in the central nervous system. As a result, mice null for caspase 3 display considerable neuronal expansion, usually resulting in death by the second week of life. Consistent with the proposal that apoptosis plays a central role in human neurodegenerative disease, caspase-3 activation has recently been observed in stroke, spinal cord trauma, head injury and Alzheimer's disease. Indeed, peptide-based caspase inhibitors prevent neuronal loss in animal models of head injury and stroke, suggesting that these compounds may be the forerunners of non-peptide small molecules that halt the apoptotic process implicated in these neurodegenerative disorders. The present review will summarise some of the recent data suggesting that apoptosis inhibitors may become a practical therapeutic approach for both acute and chronic neurodegenerative conditions.
Charriaut-Marlangue
Christiane
C
Laboratoire DVSN, UMR-CNRS 7102, Paris, France. Christiane.Marlangue@snv.jussieu.fr
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000254:growth & development; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011506:Proteins / Q000235:genetics
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D018696:Neuroprotective Agents; D011506:Proteins; D020169:Caspases