胰岛素降解酶与阿尔兹海默病的发生

The Role of the Insulin Degrading Enzyme in the Pathogenesis of Alzheimer's Disease

阿尔兹海默病(AD)是以脑中β淀粉样蛋白(Aβ)累积和神经纤维缠绕(NFTs)为主要病理特征的神经退行性疾病,而胰岛素降解酶(IDE)是人体内最主要的Aβ降解酶之一。因此,IDE在AD进程中的作用受到了研究人员的广泛关注。大多数研究显示,AD的病理进程伴随着脑中IDE编码基因的表达和IDE活性的下降。IDE敲除动物也能够表现出AD样表型,同时已有研究尝试靶向于IDE进行AD的治疗。本文通过总结IDE在AD患者和AD模型动物脑中表达情况的变化,以及IDE敲除动物的表型,对近期IDE在AD发生中作用的研究进行了总结。

Alzheimer ＇s disease（ AD） is a neurodegenerative disease characterized by extracellular amyloid plaques and intracellular neurofibrillary tangled tau proteins in the brain. As the insulin degrading enzyme（ IDE） is one of the main enzymes responsible for amyloid peptide degradation in the human body,its role in the pathogenesis of AD has been extensively investigated. Although there is some inconsistency in the results,most data suggest a decrease of IDE expression or protein functions in human and animal subjects with AD. In addition,IDE knock-out animal models are characterized by classic features of AD,which further implies that IDE is an important molecule in the pathogenesis of AD. Thus,development of IDE modulators maybe a new venue for therapeutic intervention of AD.