文章基本信息

标题：Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo
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作者：Wesley Farris ; Stefan Mansourian ; Yang Chang 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：7
页码：4162-4167
DOI：10.1073/pnas.0230450100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Two substrates of insulin-degrading enzyme (IDE), amyloid {beta}-protein (A{beta}) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively. We previously identified IDE as a principal regulator of A{beta} levels in neuronal and microglial cells. A small chromosomal region containing a mutant IDE allele has been associated with hyperinsulinemia and glucose intolerance in a rat model of DM2. Human genetic studies have implicated the IDE region of chromosome 10 in both AD and DM2. To establish whether IDE hypofunction decreases A{beta} and insulin degradation in vivo and chronically increases their levels, we characterized mice with homozygous deletions of the IDE gene (IDE -/-). IDE deficiency resulted in a >50% decrease in A{beta} degradation in both brain membrane fractions and primary neuronal cultures and a similar deficit in insulin degradation in liver. The IDE -/- mice showed increased cerebral accumulation of endogenous A{beta