β-淀粉样蛋白的代谢与调控:阿尔采末病的潜在治疗靶点

Metabolism and regulation of a-amyloid:a potential target for Alzheimer therapy

β-淀粉样蛋白(Aβ)是阿尔采末病患者脑中老年斑的主要成分,由淀粉样前体蛋白经β-分泌酶途径代谢产生。已有大量研究证明Aβ具有神经毒性,老化形成聚合体可以增强其毒性。正常生理条件下Aβ的产生和清除处于动态平衡,基因突变和外界环境的影响能破坏Aβ的动态平衡,使Aβ聚集和沉积,通过诱发氧化应激、细胞凋亡、炎症级联反应、改变兴奋性氨基酸受体等途径,引发或加速阿尔采末病的产生和发展。本文对Aβ的产生和清除、毒性及其与阿尔采末病之间的关系作一综述。

Being the main component of senile plaques in Alzheimer＇s disease （AD）, β-amyloid protein （Aβ） is derived from amyloid precursor protein via β-secretase-mediated pathway. The neurotoxicity of Aβ has been proven by abundant studies, which can be intensified by aggregation. There is a homeostasis of Aβ production and clearance in the physiological state. Genetic mutation and environment can interrupt this balance and lead to assembly and deposition of Aβ, in turn cause or accelerate the progress of AD, via oxidative stress, apoptosis, inflammation, etc. In this paper, the formation, clearance and neurotoxicity of Aβ as well as its possible role in AD are reviewed.