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exosomes from patients with parkinson’s disease are pathological in mice
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نویسنده
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han chao ,xiong nian ,guo xingfang ,huang jinsha ,ma kai ,liu ling ,xia yun ,shen yan ,li jie ,jiang haiyang ,wang luxi ,guo shiyi ,xu xiaoyun ,zhang guoxin ,liu jingyu ,cao xuebing ,zhang zhentao ,lin zhicheng ,wang tao
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منبع
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journal of molecular medicine - 2019 - دوره : 97 - شماره : 9 - صفحه:1329 -1344
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چکیده
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Cell-to-cell transport of risk molecules is a highly anticipated pathogenic mechanism in the initiation and progression of various neurodegenerative diseases. extracellular exosome-mediated neuron to neuron transport of α-synuclein (α-syn) is increasingly recognized as a potential etiologic mechanism in parkinson’s disease (pd). exosomal inflammation has also been increasingly implicated in pd pathogenesis and could trigger, facilitate, or aggravate disease development. however, these mechanisms have not been verified systematically, especially in vivo. since serum contains abundant exosomes, the correlation between serum exosomes and pd pathogenesis remains unknown. here, we show that exosomes from pd patient serum contain more α-syn and inflammatory factors such as il-1β and tnf-α than neurological normal controls, eventually cause α-syn, ubiquitin, and p62 aggregation in recipient cells. more importantly, the intravenous or intrastriatal treatment of mice with exosomes from pd patient serum could evoke protein aggregation, trigger dopamine neuron degeneration, induce microglial activation, and cause apomorphine-coaxed rotation and movement defects. all these findings imply the exosome pathway as a new pathogenesis mechanism for pd, and therefore present new targets for therapeutics.
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کلیدواژه
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parkinson’s disease ,exosomes ,α-synuclein ,pathogenesis
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آدرس
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huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china. university of science and technology of china, the first affiliated hospital of ustc, department of neurology, division of life sciences and medicine, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china. people’s hospital of dongxihu district, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, key laboratory of molecular biophysics of ministry of education, huazhong university of science and technology, college of life science and technology, centre for genome research, china, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china, renmin hospital of wuhan university, department of neurology, china, mclean hospital, harvard medical school; division of basic neuroscience, and mailman neuroscience research center, department of psychiatry, usa, huazhong university of science and technology, union hospital, tongji medical college, department of neurology, china
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Authors
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