Proteolytic processing of presenilin‐1 (PS‐1) is not associated with Alzheimer's disease with or without PS‐1 mutations

FEBS Letters

Ishii, Kazuhiko¹  Sahara, Naruhiko¹  Okochi, Masayasu¹  St. George-Hyslop, Peter H⁵  Kametani, Fuyuki¹  Martin, Jean-Jacques⁷  Tanaka, Kikuko¹  Nee, Linda E²  Ikeda, Masaki⁵  Fraser, Peter E⁵  Saunders, Ann M⁴  Van Broeckhoven, Christine⁶  Hendriks, Lydia⁶  Roses, Allen D⁴  Shoji, Shin-Ichi³  Mori, Hiroshi¹  Usami, Mihoko¹ 

[1]Department of Molecular Biology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagayaku, Tokyo 156, Japan

[2]Medical Neurology Branch, NINDS, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

[3]Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305, Japan

[4]Departments of Medicine (Neurology) and Neurobiology, Joseph and Kathleen Bryan Alzheimer Disease Research Center, Duke University Medical Center, Durham, NC 29910, USA

[5]Center for Research into Neurodegenerative Diseases, Department of Medicine (Neurology) and Medical Biophysics, University of Toronto, and Department of Medicine, Division of Neurology, The Toronto Hospital, Toronto, Ont. M5S 1A8, Canada

[6]Laboratory of Neurogenetics, Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS), University of Antwerp (UIA), Department of Biochemistry, Antwerp, Belgium

[7]Laboratory of Neuropathology, Born-Bunge Foundation (BBS), University of Antwerp (UIA), Department of Medicine, Antwerp, Belgium

关键词: Alzheimer's disease;    Presenilin;    Mutation;    Caspase-3;    CPP32;    AD;    Alzheimer's disease;    FAD;    familial AD;    PS-1;    presenilin-1;    PS-2;    presenilin-2;    NTF;    the amino-terminal fragment;    CTF;    the carboxy-terminal fragment;    SDS-PAGE;    sodium dodecyl sulfate polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(97)01378-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown