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突触的靶向补体抑制可防止脱髓鞘疾病
作者:小柯机器人 发布时间:2019/12/27 15:10:13

美国马萨诸塞大学医学院Dorothy P. Schafer小组近日取得一项新成果。他们的研究表明,突触的靶向补体抑制可在脱髓鞘疾病中防止小胶质突触吞噬和的突触丢失。这一研究成果于2019年12月26日在线发表于国际学术期刊《免疫》。

研究人员使用死后人类多发性硬化症(MS)组织、MS的临床前非人类灵长类动物模型和两个脱髓鞘疾病的啮齿动物模型,研究了视觉系统中突触的变化。类似于其他神经退行性疾病,研究人员观察到小胶质突触吞噬和严重的突触损失。在小鼠中,突触丢失与局部脱髓鞘和神经元变性无关,但与神经胶质增生和突触中补体成分C3(而非C1q)增加有关。C3结合突触的补体抑制剂Crry的病毒过表达减少了突触的小胶质细胞吞噬并保护了视觉功能。

这些结果表明,小胶质细胞通过脱髓鞘疾病的替代补体级联来消除突触,并确定了一种可以广泛应用于其他神经退行性疾病的防止突触丧失的策略。

据悉,MS是中枢神经系统的脱髓鞘性自身免疫性疾病。虽然研究的重点是MS中的髓磷脂和轴突损失,但对突触改变的潜在机制了解较少。

附:英文原文

Title: Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease

Author: Sebastian Werneburg, Jonathan Jung, Rejani B. Kunjamma, Seung-Kwon Ha, Nicholas J. Luciano, Cory M. Willis, Guangping Gao, Natalia P. Biscola, Leif.A. Havton, Stephen J. Crocker, Brian Popko, Daniel S. Reich, Dorothy P. Schafer

Issue&Volume: December 26, 2019

Abstract: Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on myelin and axon loss in MS, less is known about mechanisms underlying synaptic changes. Using postmortem human MS tissue, a preclinical nonhuman primate model of MS, and two rodent models of demyelinating disease, we investigated synapse changes in the visual system. Similar to other neurodegenerative diseases, microglial synaptic engulfment and profound synapse loss were observed. In mice, synapse loss occurred independently of local demyelination and neuronal degeneration but coincided with gliosis and increased complement component C3, but not C1q, at synapses. Viral overexpression of the complement inhibitor Crry at C3-bound synapses decreased microglial engulfment of synapses and protected visual function. These results indicate that microglia eliminate synapses through the alternative complement cascade in demyelinating disease and identify a strategy to prevent synapse loss that may be broadly applicable to other neurodegenerative diseases.

DOI: 10.1016/j.immuni.2019.12.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30523-0

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx