Caspase-9.
Caspase-9 is a member of caspase family of cysteine proteases that have been implicated in apoptosis and cytokine processing. When cells receive apoptotic stimuli, mitochondria releases cytochrome c which then binds to Apaf-1, the mammalian Ced-4 homologue, together with dATP. The resultant complex recruits Caspase-9 leading to its activation. Activated Caspase-9 cleaves downstream caspases such as Caspase-3, -6 and -7 initiating the caspase cascade. The majority of homozygous Caspase-9 null mice die perinatally with a markedly enlarged and malformed cerebrum caused by a reduction of apoptosis during early brain development. Thus, Caspase-9 function is essential for apoptosis during normal development of the central nervous system. These data suggest that inhibition of Caspase-9 activity would render opportunity to treat patients suffering from neurological diseases such as stroke, neurodegenerative diseases or brain injury caused by hypoxia.
Kuida
K
K
Genomic Pharmacology Group, Vertex Pharmaceuticals, Cambridge, MA 02139, USA. kuida@vpharm.com
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology
C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases