Regulation of Amyloidogenesis and Clearance of p-Amyloid in Alzheimer' s Disease / 中国生物化学与分子生物学报

ABSTRACT

Alzheimer ' s disease (AD ) , an age-associated chronic progressive neurodegeneration disorder, is characterized by progressive loss of memory, cognitive impairment and behavioral changes.The pathological hallmarks of AD are (3-amyloid (A(3) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, upregulation of inflammation and neuronal apoptosis.Amyloid is a polypeptide consisting of 39-42 amino acids which is produced by a series of enzymatic hydrolysis of amyloid precursor protein in neurons.Studying the regulation of the production and clearance of Ais of great importance which may help in finding potential intervention to effectively delay or even reverse the process of Alzheimer's disease.As the key enzyme of A(3 production, (3-secretase ((3-site APP cleaving enzyme 1, BACE'l) plays an essential role in the development of AD.The aggregation of inflammatory cells around senile plaques suggests that A(3 is highly associated with neuroinflammation.Neuroinflammation-related cells participate in the clearance of A(3 and multiple cytokines regulate the level of A0.In addition, although non-coding UNA is rarely involved in the production, deposition and clearance of A(3 directly, it can regulate the production of A(3 through other pathways.In this article, we will focus on the important role of BACE1, neuroinflammation and non-coding RNA in the regulation of A(3 and review the mechanism of production and clearance of A(3 in AD.