Amyloid metabolism and secretases in Alzheimer's disease.

被引：24
作者：
Xia W. [1 ]
机构：
[1] Center for Neurologic Diseases, Brigham and Women's Hospital, HIM 616, 77 Avenue Louis Pasteur, Boston, 02115, MA
来源：
Current Neurology and Neuroscience Reports | 2001年 / 1卷 / 5期
关键词：
Tace; Amyloid Precursor Protein; Aspartyl Protease; Amyloid Precursor Protein Transgenic Mouse; Amyloid Metabolism;
D O I：
10.1007/s11910-001-0101-z
中图分类号：
学科分类号：
摘要：
Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid fibrils composed of the amyloid beta-protein (A beta) in senile plaques. A beta is derived from the beta-amyloid precursor protein (APP) after beta- and gamma-secretase cleavages. beta-secretase was recently identified to be a membrane-anchored aspartyl protease that is widely distributed in subcellular compartments, including Golgi, trans-Golgi network, and endosomes. Although definitive identification of gamma-secretase will require reconstituting its activity in vitro, mounting evidence suggests that gamma-secretase is an unusual intramembrane-cleaving aspartyl protease. Two intramembranous aspartate residues in presenilin (PS) are absolutely required for A beta generation. Three classes of gamma-secretase inhibitors can directly bind to PS, strongly supporting the hypothesis of PSI as gamma-secretase. These results provide the molecular basis for therapeutic interventions that reduce A beta accumulation in AD patients by inhibiting beta- or gamma-secretase.
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收藏
页码：422 / 427
页数：5
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