| Literature DB >> 10319819 |
F G Gervais1, D Xu, G S Robertson, J P Vaillancourt, Y Zhu, J Huang, A LeBlanc, D Smith, M Rigby, M S Shearman, E E Clarke, H Zheng, L H Van Der Ploeg, S C Ruffolo, N A Thornberry, S Xanthoudakis, R J Zamboni, S Roy, D W Nicholson.
Abstract
The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer's disease brains and colocalization of its APP cleavage product with A beta in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease.Entities:
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Year: 1999 PMID： 10319819 DOI： 10.1016/s0092-8674(00)80748-5
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582