The γ-secretase complex:: machinery for intramembrane proteolysis

被引：143

作者：

Iwatsubo, T ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo 1130033, Japan

来源：

CURRENT OPINION IN NEUROBIOLOGY | 2004年 / 14卷 / 03期

关键词：

D O I：

10.1016/j.conb.2004.05.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

gamma-Secretase is a membrane protease complex that possesses presenilin as a catalytic subunit. Presenilin generates amyloid 0 pepticles in the brains of Alzheimer's patients and is indispensable to Notch signaling in tissue development and renewal. Recent studies have revealed how presenilin is assembled with its cofactor proteins and acquires the gamma-secretase activity: Aph-1 and nicastrin initially form a subcomplex to bind and stabilize presenilin, and then Pen-2 confers the gamma-secretase activity and facilitates endoproteolysis of presenilin. Understanding the mechanism of gamma-secretase cleavage will help to clarify how intercellular cell signaling through transmembrane proteins is regulated by intramembrane proteolysis, and will hopefully eventually lead to a cure for Alzheimer's disease.

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收藏

页码：379 / 383

页数：5

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