文章基本信息

标题：Amyloid-β peptide levels in brain are inversely correlated with insulysin activity levels in vivo
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作者：Bonnie C. Miller ; Elizabeth A. Eckman ; Kumar Sambamurti 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：10
页码：6221-6226
DOI：10.1073/pnas.1031520100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Factors that elevate amyloid-{beta} (A{beta}) peptide levels are associated with an increased risk for Alzheimer's disease. Insulysin has been identified as one of several proteases potentially involved in A{beta} degradation based on its hydrolysis of A{beta} peptides in vitro. In this study, in vivo levels of brain A{beta}40 and A{beta}42 peptides were found to be increased significantly (1.6- and 1.4-fold, respectively) in an insulysin-deficient gene-trap mouse model. A 6-fold increase in the level of the {gamma}-secretase-generated C-terminal fragment of the A{beta} precursor protein in the insulysin-deficient mouse also was found. In mice heterozygous for the insulysin gene trap, in which insulysin activity levels were decreased {approx}50%, brain A{beta} peptides were increased to levels intermediate between those in wild-type mice and homozygous insulysin gene-trap mice that had no detectable insulysin activity. These findings indicate that there is an inverse correlation between in vivo insulysin activity levels and brain A{beta} peptide levels and suggest that modulation of insulysin activity may alter the risk for Alzheimer's disease.