泛素-蛋白酶体系统与阿尔茨海默病

The ubiquitin-proteasome system and Alzheimer's disease

阿尔茨海默病(Alzheimer's disease,AD)是常见的神经退行性疾病,其主要病理特征是神经元外β-淀粉样蛋白沉积导致的老年斑和神经元内神经元纤维缠结的形成。泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)是蛋白质降解的主要途径之一,也是清除异常蛋白和防止神经元内异常蛋白聚集的关键。泛素化蛋白的积累和聚集是许多神经退行性疾病的标志。AD患者脑中UPS功能障碍与β-淀粉样蛋白沉积、Tau蛋白磷酸化、突触功能低下和载脂蛋白E均有密切的关系,UPS在AD的发病机制中备受关注。因此,调控UPS及其相关蛋白的功能对AD有改善作用,可能是治疗AD的潜在靶点。本文就泛素-蛋白酶系统功能障碍与阿尔茨海默病之间的关系做一综述,为阿尔茨海默病的治疗提供新的方向。

Alzheimer’s disease(AD)is a common neurodegenerative disease,the main pathological characterized by senile plaques caused by the deposition ofβ-amyloid and the formation of neurofibrillary tangles in the brain.As one of the main pathways for protein degradation,the ubiquitin-proteasome system(UPS)serves as the key factor to remove abnormal proteins and prevent abnormal proteins accumulation in neurons.It was reported that accumulation and aggregation of ubiquitin in the brain are important symbols in many neurodegenerative diseases.Increasing evidences have shown that UPS dysfunction in the brains of Alzheimer’s sufferers can facilitateβ-amyloid deposition and Tau phosphorylation,deteriorate the functions of synapse and apolipoprotein E.Until recently,UPS has attracted much attention in the pathogenesis of AD.Therefore,regulating the function of UPS and its related proteins have therapeutic effects on AD,and may be a potential target for the treatment of AD.In this paper,we review the relationship between the dysfunction of UPS and AD,providing a new strategy for the treatment of AD.