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

被引：9
作者：
Yang, Weiwei [1 ,2 ]
Yu, Wenjiao [1 ,2 ]
Li, Xuran [1 ,2 ]
Li, Xin [1 ,2 ]
Yu, Shun [1 ,2 ,3 ]
机构：
[1] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Neurobiol, Beijing, Peoples R China
[2] Beijing Inst Brain Disorders, Ctr Parkinsons Dis, Beijing, Peoples R China
[3] Beijing Key Lab Parkinsons Dis, Beijing, Peoples R China
来源：
NEUROBIOLOGY OF AGING | 2020年 / 90卷
关键词：
Aging; Brain; alpha-Synuclein; NMDA receptor; Internalization; LEVODOPA-INDUCED DYSKINESIAS; NMDA RECEPTOR; AGE; SUBUNIT; MEMORY; OLIGOMERS; NEURONS; PHOSPHORYLATION; INHIBITION; BETA;
D O I：
10.1016/j.neurobiolaging.2020.02.015
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
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 alpha-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-alpha-synuclein exhibited a stronger correlation with the expression of surface GluN1 and total Rab5B. In MES23.5 cells, the monomer- or oligomer-alpha-synuclein were shown to increase in a manner dependent on the concentrations of the added monomers and oligomers. Again, the oligomer-alpha-synuclein showed more potent effects than the monomer-alpha-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 alpha-synuclein monomers and oligomers differentially contributes to the reduction in surface NMDAR expression in selective brain regions. (C) 2020 Elsevier Inc. All rights reserved.
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页码：24 / 32
页数：9
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