Parkinson's disease: From genetics to molecular dysfunction and targeted therapeutic approaches

作     者：Yue Huang Jun Wei Antony Cooper Margaret J.Morris Yue Huang;Jun Wei;Antony Cooper;Margaret J.Morris

作者机构：China National Clinical Research Center for Neurological DiseasesBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of PharmacologySchool of Medical SciencesFaculty of Medicine&HealthUNSWSydneyNSW 2052Australia The Garvan Institute of Medical ResearchSydneyNSW 2010Australia St Vincent's Clinical SchoolFaculty of Medicine&Healthand School of Biotechnology and Biomolecular SciencesFaculty of ScienceUNSWSydneyNSW 2052Australia 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2023年第10卷第3期

页      面：786-798页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by National Natural Science Foundation of China(No.NSFC 82071417,YH) AC received grant funding from the Australian government 

主　　题：Drug discovery Genetics Molecular function Parkinson's disease Quantitative traits 

摘      要：Parkinson s disease (PD) is the most common neurodegenerative movement disorder in the elderly. As the pathogenesis of PD is still not fully understood, medications with the capacity of halting the disease progression are currently unavailable. The discovery of genes that are causative for, or increase susceptibility to PD is pivotal for the development of novel therapeutic approaches, as they are critical for the onset of PD and the molecular pathways underlying its pathogenesis. By reviewing relevant data, we discuss causative genes, and those associated with PD susceptibility and quantitative traits. Through Gene Ontology database and STRING analysis, we emphasize the roles of inorganic cation transmembrane transport pathways and hypothalamic pituitary thyroid axis, in addition to the established roles of inflammation/oxidative stress and mitochondrial dysfunction in the pathogenesis of PD. It is hoped these insights 1) untangle the clinical complex presentations of PD, 2) reveal the interwoven molecular network leading to PD, and 3) identify critical molecular targets to facilitate novel PD drug discovery, with a view to providing improved consultation and personalized medicine for patients with PD in the future.