摘要
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.
作者
盛婵娟
王越
臧彩霞
张自弘
鲍秀琦
张丹
SHENG Chan-juan;WANG Yue;ZANG Cai-xia;ZHANG Zi-hong;BAO Xiu-qi;ZHANG Dan(State Key Laboratory of Natural Products and Functions,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第7期798-803,共6页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项资助项目(2018ZX09711001-008-005
2018ZX09711001-003-020)
国家自然科学基金资助项目(81773718
81630097)
中国医学科学院医学与健康科技创新工程资助项目(2016-I2M-3-011)
中国医学科学院院所基本科研业务费资助项目(2018RC350002)