Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson’s disease in Drosophila

作     者：Wei Liu Kah-Leong Lim Eng-King Tan 

作者机构：School of Plant ProtectionAnhui Province Key Laboratory of Crop Integrated Pest ManagementAnhui Province Engineering Laboratory for Green Pesticide Development and ApplicationAnhui Agricultural UniversityHefei 230036China Department of NeurologyNational Neuroscience InstituteSingapore 308433Singapore Department of ResearchNational Neuroscience InstituteSingaporeSingapore ResearchLee Kong Chian School of Medi-cineSingaporeSingapore Neuroscience and Behavioural Disorders ProgramDuke-NUS Medical SchoolSingapore 169857Singapore. 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2022年第11卷第1期

页      面：262-279页

核心收录：

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

基　　金：the Singapore Ministry of Health’s National Medical Research Council under its Singapore Translational Research(STaR)Investigator Award(NMRC/STaR/0030/2018) National Parkinson’s Disease Translational Clinical Research Programme(013-NNI/2014) National Medical Research Council Singapore,OF LCG 000207,SPARKS II,and Innovative Research Group Project of the the National Natural Science Foundation of China(31501175) Talents in Anhui Agricultural University(RC342201) 

主　　题：Intestine α-Synuclein Parkinson’s disease Microbiome 

摘      要：Background:Aberrant aggregation ofα-synuclein(α-syn)is a key pathological feature of Parkinson’s disease(PD),but the precise role of intestinalα-syn in the progression of PD is *** a number of genetic Drosophila models of PD,α-syn was frequently ectopically expressed in the neural system to investigate the ***:We investigated the potential role of intestinalα-syn in PD pathogenesis using a Drosophila ***α-syn was overexpressed in Drosophila guts,and life span,survival,immunofluorescence and climbing were ***,Western blotting and reactive oxygen species(ROS)staining were performed to assess the effects of intestinalα-syn on intestinal ***‐throughput RNA and 16S rRNA gene sequencing,quantitative RT‐PCR,immunofluorescence,and ROS staining were performed to determine the underlying molecular ***:We found that the intestinalα-syn alone recapitulated many phenotypic and pathological features of PD,including impaired life span,loss of dopaminergic neurons,and progressive motor *** intestine-derivedα-syn disrupted intestinal homeostasis and accelerated the onset of intestinal ***,intestinal expression ofα-syn induced dysbiosis,while microbiome depletion was efficient to restore intestinal homeostasis and ameliorate the progression of ***α-syn triggered ROS,and eventually led to the activation of the dual oxidase(DUOX)-ROS-Jun N-terminal Kinase(JNK)*** addition,α-syn from both the gut and the brain synergized to accelerate the progression of ***:The intestinal expression ofα-syn recapitulates many phenotypic and pathologic features of PD,and induces dysbiosis that aggravates the pathology through the DUOX-ROS-JNK pathway in *** findings provide new insights into the role of intestinalα-syn in PD pathophysiology.