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  • Title: Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease.
    Author: Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE.
    Journal: Science; 1997 Jul 18; 277(5324):373-6. PubMed ID: 9219695.
    Abstract:
    Most cases of early-onset familial Alzheimer's disease (FAD) are caused by mutations in the genes encoding the presenilin 1 (PS1) and PS2 proteins, both of which undergo regulated endoproteolytic processing. During apoptosis, PS1 and PS2 were shown to be cleaved at sites distal to their normal cleavage sites by a caspase-3 family protease. In cells expressing PS2 containing the asparagine-141 FAD mutant, the ratio of alternative to normal PS2 cleavage fragments was increased relative to wild-type PS2-expressing cells, suggesting a potential role for apoptosis-associated cleavage of presenilins in the pathogenesis of Alzheimer's disease.
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