1. Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations
- Author
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Naruhiko Sahara, M. Ikeda, Linda E. Nee, Kikuko Tanaka, Jean-Jacques Martin, Christine Van Broeckhoven, Peter E Fraser, Allen D. Roses, Peter St George-Hyslop, Masayasu Okochi, Kazuhiko Ishii, Ann M. Saunders, Fuyuki Kametani, Mihoko Usami, Shin'ichi Shoji, L. Hendriks, and Hiroshi Mori
- Subjects
Molecular Sequence Data ,Biophysics ,Caspase 3 ,Disease ,Biology ,medicine.disease_cause ,Biochemistry ,Presenilin ,Mice ,Alzheimer Disease ,Structural Biology ,Presenilin-1 ,Genetics ,medicine ,Animals ,Humans ,Point Mutation ,Amino Acid Sequence ,Fragmentation (cell biology) ,Molecular Biology ,Polyacrylamide gel electrophoresis ,Cerebral Cortex ,Mutation ,Brain ,Membrane Proteins ,Cell Biology ,Alzheimer's disease ,Molecular biology ,Cysteine protease ,Peptide Fragments ,Caspase-3 ,Apoptosis ,CPP32 ,Rabbits ,Protein Processing, Post-Translational - Abstract
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.
- Published
- 1997
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