Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease  

作　　者：Zhi Dong Zhou Thevapriya Selvaratnam Ji Chao Tristan Lee Yin Xia Chao Eng-King Tan 

机构地区：[1]Department of Research,National Neuroscience Institute,11 Jalan Tan Tock Seng,Singapore 308433,Singapore [2]Department of Neurology,Singapore General Hospital,Outram Road,Singapore 169608,Singapore [3]Signature Research Program in Neuroscience and Behavioural Disorders,Duke-NUS Medical School Singapore,8 College Road,Singapore,Singapore

出　　处：《Translational Neurodegeneration》2019年第1期63-76,共14页转化神经变性病（英文）

基　　金：The Singapore National Medical Research Council(NMRC)grants including STaR and a clinical translational research program in Parkinson’s disease.

摘　　要：Parkinson’s disease(PD)is the most common neurodegenerative movement disorder,which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas.The detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear,and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD.However,the formation ofα-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD,possibly stemming from the consequence of protein misfolding and dysfunctional proteostasis.Proteostasis is the mechanism for maintaining protein homeostasis via modulation of protein translation,enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and autophagy.Deregulated protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes,leading to pathological protein aggregation and neurodegeneration in PD.In recent years,multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been identified.The potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

关 键 词：Molecular targets Neuron degeneration Parkinson’s disease Protein aggregation Protein translation PROTEOSTASIS 

分 类 号：H31[语言文字—英语]