Targeting endogenous inhibitors of apoptosis for treatment of cancer, stroke and multiple sclerosis.
The inhibitor of apoptosis (IAP) genes have emerged as probably the most important intrinsic regulators of apoptosis. The members of the IAP family are highly conserved in evolutionarily distant species and perform the critical role of binding to and inhibiting distinct caspases. This inhibition is mediated by discrete baculoviral IAP repeat domains that, in a domain-specific manner, inhibit either the initiator or executioner caspases. As such the function of IAPs lies at the very centre of virtually all apoptotic pathways. Since many, if not most, human pathologies involve aberrant apoptosis, the modulation of IAP levels or their activity offers huge therapeutic potential for treatment of various disorders. Indeed, available data suggest that the therapeutic downregulation of IAPs by antisense targeting or their adenovirally-mediated overexpression, can in fact be used to successfully modulate cell death.
Holcík
Martin
M
Apoptosis Research Center, Children's Hospital of Eastern Ontario Research Institute and Department of Pediatrics, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, K1H 8L1, USA. martin@mgcheo.med.uottawa.ca
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*
D051034:Inhibitor of Apoptosis Proteins