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Alpha-synuclein oligomerization and dopaminergic degeneration occur synchronously in the brain and colon of MPTP-intoxicated parkinsonian monkeys.

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机构: [a]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China [b]National Clinical Research Center for Geriatric Disorders, Beijing, China [c]Laboratory of Neuroscience, Affiliated Hospital of Guilin Medical University, Guilin, China [d]Department of Neurology, Beijing Daxing District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
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Dopaminergic (DAergic) degeneration and abnormal α-synuclein (α-syn) expression, phosphorylation and aggregation are observed in both the nigrostriatal system (NSS) and enteric nervous system (ENS) of patients with Parkinson's disease (PD). Whether these alterations in α-syn and DAergic neurons occur synchronously in the two nervous systems or follow a process that spreads from the gut to the brain remains a subject of debate. Here, in MPTP-intoxicated cynomolgus monkeys, we showed a parallel DAergic degeneration in the colon as well as in the substantia nigra and striatum (SN/STR), as indicated by reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). In addition, we observed a simultaneous increase in the concentrations of total, phosphorylated, and oligomeric α-syn in the colon and SN/STR. Moreover, we identified that the above changes in α-syn were associated with an increase in the expression of polo-like kinase 2 (PLK2), an enzyme that promotes α-syn phosphorylation, and a decrease in the activity of protein phosphatase 2A (PP2A), an enzyme that facilitates α-syn dephosphorylation. Because the colonic ENS can be readily analyzed using routine biopsies, the shared pathological features between the colonic ENS and the brain NSS found in this study provide useful information for assessing and understanding the neuropathology in PD patients using colonic biopsies. Copyright © 2019. Published by Elsevier B.V.

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出版当年[2019]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
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出版当年[2018]版:
Q3 NEUROSCIENCES
最新[2023]版:
Q3 NEUROSCIENCES

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第一作者机构: [a]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China [b]National Clinical Research Center for Geriatric Disorders, Beijing, China
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通讯机构: [a]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China [b]National Clinical Research Center for Geriatric Disorders, Beijing, China
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