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Proteolytic processing of presenilin‐1 (PS‐1) is not associated with Alzheimer's disease with or without PS‐1 mutations
Author(s) -
Okochi Masayasu,
Ishii Kazuhiko,
Usami Mihoko,
Sahara Naruhiko,
Kametani Fuyuki,
Tanaka Kikuko,
Fraser Peter E,
Ikeda Masaki,
Saunders Ann M,
Hendriks Lydia,
Shoji Shin-Ichi,
Nee Linda E,
Martin Jean-Jacques,
Van Broeckhoven Christine,
St. George-Hyslop Peter H,
Roses Allen D,
Mori Hiroshi
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01378-1
Subject(s) - presenilin , microbiology and biotechnology , apoptosis , caspase , alzheimer's disease , mutation , cysteine , protease , fragmentation (computing) , chemistry , caspase 3 , biology , cysteine protease , genetics , biochemistry , gene , programmed cell death , enzyme , disease , medicine , pathology , ecology
Cerebral presenilin‐1 protein (PS‐1) is normally composed of the amino‐terminal fragment (NTF) with M r 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.