中性内肽酶在阿尔茨海默病发病机制中的作用  

Role of Neprilysin in The Pathogenesis of Alzheimer′s Disease

作　　者：杨红旗[1,2] 邢莹[3] 

机构地区：[1]河南省人民医院神经内科,郑州450003 [2]郑州大学人民医院神经内科,郑州450003 [3]郑州大学基础医学院生理学教研室,郑州450052

出　　处：《生物化学与生物物理进展》2012年第8期721-725,共5页Progress In Biochemistry and Biophysics

基　　金：河南省重点科技攻关计划项目(112102310684)~~

摘　　要：β-淀粉样蛋白(βamyloid,Aβ)在海马区的沉积是阿尔茨海默病(Alzheimer′s disease,AD)发病的典型表现,清除或降低Aβ含量是治疗AD的目标之一.较之Aβ生成的增多,体内降解Aβ能力的下降在AD发病过程中显得更为重要.尽管Aβ在体内可以通过运输到血液和脑脊液途径来清除,但大部分Aβ被中性内肽酶(neprilysin,NEP)为代表的一类蛋白酶降解为小分子后从体内清除.老年人、轻度认知障碍期(MCI)和AD患者的NEP活性显著下降,且NEP活性下降与脑内Aβ升高及AD患者认知功能损伤相关.NEP有可能成为AD治疗的潜在药物靶点,针对轻度认知障碍前期(pre-MCI)和MCI,提高NEP的活性,促进Aβ的降解,有可能延缓AD的发生和发展.Deposition of β amyloid （Aβ） in hippocampus is a crucial progression in the pathophysiology of Alzheimer＇s disease （AD）. Decreasing its formation and/or increasing its clearance have become a focus of AD therapy. As compared with increased Aβ production, decreased Aβ degradation plays a more important role in AD pathogenesis. Although Aβ can be cleared through transportation to the blood and cerebral spinal fluid pathway, the so-called ＂vascular system＂, most Aβ peptide was degraded to small molecules by a kind ofprotease called Aβ degrading enzyme represented by neprilysin （NEP）. In the olderly, mild cognitive impairment and AD patients, the NEP activity is decreased, and the decreased NEP activity is correlated with Aβ content in brain and cognitive function impairment. If NEP activity was increased to degrade Aβ, it may inhibit AD progression and even have disease-modifying potential in AD and NEP thus may behave as a potential drug target for AD therapy.

关 键 词：阿尔茨海默病 Aβ降解酶 中性内肽酶 Β-淀粉样蛋白 

分 类 号：R749.1[医药卫生—神经病学与精神病学]