β-淀粉样前体蛋白裂解途径及截断型β-淀粉样蛋白对阿尔茨海默病的影响

Effect of processing pathway of amyloid precursor protein and truncated amyloid-β protein on Alzheimer’s disease

阿尔茨海默病(Alzheimer disease’s,AD)是以老年斑(senile plaques,SPs)、神经原纤维缠结(neurofibrillary tangles,NFTs)等为主要病理特征的神经退行性疾病。β-淀粉样蛋白(β-amyloid protein,Aβ)在神经元胞外聚集形成老年斑,是引起AD的关键因素。过量Aβ的产生来源于β-淀粉样前体蛋白(β-amyloid precursor protein,APP)裂解途径的异常。因此,探究APP在AD的发病过程中裂解途径及Aβ的产生机制具有重要意义。目前,很多药物研究以减少和清除老年斑为目的,但是老年斑的形成是由全长Aβ和多种截断型Aβ共同作用的结果,并且其对SPs形成的影响作用机制尚未完全明确。本文就APP裂解途径及截断型Aβ的产生机制进行综述,以期为AD的研究提供理论依据。

Alzheimer’s disease(AD)is a neurodegenerative disease characterized by senile plaques(senile plaques,SPs)and neurofibrillary tangle formation.The extracellular aggregation ofβ-amyloid proteins in neurons will form senile plaques,which are the key factor to cause AD.The excessive generation ofβ-amyloid protein(Aβ)originates from abnormal processing ofβ-amyloid precursor protein(APP).Therefore,it is of great significance to explore the cleavage pathway of APP in the pathogenesis of AD and the mechanism of Aβgeneration.At present,many studies aim at reducing and clearing senile plaques.However,the formation of senile plaques is the result of interaction of full-length Aβand a variety of truncated Aβ,and the mechanism on SPs formation is not fully clear.In this review,we summarized the APP processing pathway and the mechanism of truncated Aβgeneration to provide theoretical basis for AD research.