Caspase-9

Caspase-9 is a member of caspase family of cysteine proteases that have bee n implicated in apoptosis and cytokine processing. When cells receive apopt otic 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 d ownstream caspases such as Caspase-3, -6 and -7 initiating the caspase casc ade. 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 da ta suggest that inhibition of Caspase-9 activity would render opportunity t o treat patients suffering from neurological diseases such as stroke, neuro degenerative diseases or brain injury caused by hypoxia. (C) 2000 Elsevier Science Ltd. All rights reserved.