Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations.
Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were found to be cleaved into two fragments of NTF and CTF independently of the occurrence of PS-1 mutation in human brains. A small portion of PS-1 was recently found to suffer another processing by caspase-3, an apoptosis-related cysteine protease. In contrast to the recent finding that the Volga-German mutation on presenilin-2 (PS-2) affects the increasing caspase-3 PS-2 fragment, the PS-1 mutation did not cause a significant change in PS-1 fragmentation. We conclude that PS-1 fragmentation and other (probably caspase-3-mediated) digestion following apoptosis occur independently of PS-1 mutations.
Okochi, M; Ishii, K; Usami, M; Sahara, N; Kametani, F; Tanaka, K; Fraser, PE; Ikeda, M; Saunders, AM; Hendriks, L; Shoji, SI; Nee, LE; Martin, JJ; Van Broeckhoven, C; St George-Hyslop, PH; Roses, AD; Mori, H
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