A new paradigm for neurotoxicity by FAD mutants of βAPP:: A signaling abnormality

被引：20

作者：

Nishimoto, I ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Pharmacol & Neurosci, Shinjuku Ku, Tokyo 160, Japan

来源：

NEUROBIOLOGY OF AGING | 1998年 / 19卷 / 01期

关键词：

beta APp; transmembrane configuration; signal transduction; G(o) protein; G beta gamma; apoptosis; familial; Alzheimer's disease; autoactivation;

D O I：

10.1016/S0197-4580(98)00040-2

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

We have demonstrated that normal beta APP(695) behave as a signaling receptor and indicated that point mutations at V642 create autoactive beta APP in signal transduction. Cellular expression of those familial Alzheimer's disease-associated mutants causes neuronal cells to undergo apoptotic death; and procedures inhibiting the signal of normal beta APP block the mutant-induced apoptosis. We have also shown that the mutant-induced death is mediated by intracellular G protein activity but not by secretion of A beta peptides. Accordingly, the mutant-induced death requires a cytoplasmic domain but not the 41st and 42nd residues of the A beta region. These studies provide a novel insight that beta APP may play a normal role as a death receptor and that Alzheimer's disease-relevant abnormality occurred in this function may lead neurons to suicidal degeneration. (C) 1998 Elsevier Science Inc.

引用

页码：S33 / S38

页数：6

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