疾病机制：阿尔茨海默病的新治疗策略——靶向脂筏中的淀粉样前体蛋白加工
Mechanisms of disease: new therapeutic strategies for Alzheimer's disease--targeting APP processing in lipid rafts.
作者信息
Cheng Haipeng, Vetrivel Kulandaivelu S, Gong Ping, Meckler Xavier, Parent Angèle, Thinakaran Gopal
机构信息
University of Chicago, IL, USA.
出版信息
Nat Clin Pract Neurol. 2007 Jul;3(7):374-82. doi: 10.1038/ncpneuro0549.
Abstract
Alzheimer's disease (AD) is the most common cause of age-related dementia. Pathologically, AD is characterized by the deposition in the brain of amyloid-beta peptides derived from proteolysis of amyloid precursor protein (APP) by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. A growing body of evidence implicates cholesterol and cholesterol-rich membrane microdomains in amyloidogenic processing of APP. Here, we review recent findings regarding the association of BACE1, gamma-secretase and APP in lipid rafts, and discuss potential therapeutic strategies for AD that are based on knowledge gleaned from the membrane environment that fosters APP processing.
摘要
阿尔茨海默病（AD）是与年龄相关的痴呆症最常见的病因。在病理上，AD的特征是淀粉样前体蛋白（APP）经β-位点APP裂解酶1（BACE1）和γ-分泌酶蛋白水解产生的β-淀粉样肽在大脑中沉积。越来越多的证据表明胆固醇和富含胆固醇的膜微区参与了APP的淀粉样生成过程。在此，我们综述了关于BACE1、γ-分泌酶和APP在脂筏中关联的最新研究发现，并讨论了基于从促进APP加工的膜环境中获得的知识而制定的AD潜在治疗策略。
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