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Alpha-synuclein differentially reduces surface expression of N-methyl-D-aspartate receptors in the aging human brain

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机构： [a]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China [b]Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China [c]Beijing Key Laboratory for Parkinson's Disease, Beijing, China

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关键词： Aging Brain Internalization NMDA receptor α-Synuclein

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The aging brain is associated with reduced cell surface expression of N-methyl-d-aspartate receptors (NMDARs), but the mechanism remains poorly understood. In the present study, we showed that in the striatum and hippocampus but not the cerebellum and parietal cortex, levels of α-synuclein monomers and oligomers increased with age, which correlated negatively with the expression of GluN1, and positively with the expression of total Rab5B. The oligomer-α-synuclein exhibited a stronger correlation with the expression of surface GluN1 and total Rab5B. In MES23.5 cells, the monomer- or oligomer-α-synuclein were shown to increase in a manner dependent on the concentrations of the added monomers and oligomers. Again, the oligomer-α-synuclein showed more potent effects than the monomer-α-synuclein on surface GluN1 and total Rab5B expression. Accordingly, the oligomer-treated cells showed a greater reduction in NMDA-evoked Ca2+ influx than the monomer-treated cells, which was largely inhibited by pistop2, a clathrin inhibitor. These results suggest that the age-dependent accumulation of α-synuclein monomers and oligomers differentially contributes to the reduction in surface NMDAR expression in selective brain regions. © 2020 Elsevier Inc.

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出版当年[2019]版：

大类 | 2 区医学

小类 | 2 区老年医学 2 区神经科学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区老年医学 3 区神经科学

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出版当年[2018]版：

Q1 GERIATRICS & GERONTOLOGY Q1 NEUROSCIENCES

最新[2023]版：

Q2 GERIATRICS & GERONTOLOGY Q2 NEUROSCIENCES

影响因子： 3.7 最新[2023版] 4.1 最新五年平均 4.398 出版当年[2018版] 4.905 出版当年五年平均 4.454 出版前一年[2017版] 4.347 出版后一年[2019版]

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