Degradation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: Involvement of insulin-degrading enzyme

被引：157
作者：
McDermott, JR
Gibson, AM
机构：
[1] MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, Westgate Road
来源：
NEUROCHEMICAL RESEARCH | 1997年 / 22卷 / 01期
关键词：
beta-amyloid protein; Alzheimer's disease; insulin-degrading enzyme; human brain; cathepsin D;
D O I：
10.1023/A:1027325304203
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We examined the degradation of Alzheimer's beta-amyloid protein (1-40) by soluble and synaptic membrane fractions from post mortem human and fresh rat brain using HPLC. Most of the activity at neutral pH was in the soluble fraction. The activity was thiol and metal dependent, with a similar inhibition pro file to insulin-degrading enzyme. Immunoprecipitation of insulin-degrading enzyme from the human soluble fraction using a monoclonal antibody removed over 85% of the beta-amyloid protein degrading activity. Thus insulin-degrading enzyme is the main soluble beta-amyloid degrading enzyme at neutral pH in human brain. The highest beta-amyloid protein degrading activity in the soluble fractions occurred between pH 4-5, and this activity was inhibited by pepstatin, implicating an aspartyl protease. Synaptic membranes had much lower beta-amyloid protein degrading activity than the soluble fraction. EDTA (2mM) caused over 85% inhibition of the degrading activity but inhibitors of endopeptidases -24.11, -24.15, -24.16, angiotensin converting enzyme, aminopeptidases, and carboxypeptidases had little or no effect.
引用
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页码：49 / 56
页数：8
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