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肠道接种的α-Syn可能导致PD
作者:小柯机器人 发布时间:2020/2/18 15:41:51

美国加州理工学院的Viviana Gradinaru研究组研究发现肠道接种的α-突触核蛋白(α-Syn)原纤维明确促进老年小鼠的肠道功能障碍和脑病理。2020217日,《自然神经科学》在线发表了这一成果。

有证据表明,α-Syn聚集可以起源于周围组织,并通过自主神经纤维发展到大脑。他们用α-Syn预制原纤维接种小鼠的十二指肠壁来测试这一点。接种后,他们观察到胃肠道缺陷和肠道神经系统的生理变化。使用AAV-PHP.S衣壳靶向溶酶体酶葡萄糖苷脂酶进行外周基因转移,他们发现由于该蛋白表达的增加,α-Syn病理得以减少。最后,在老年小鼠而非幼龄小鼠中接种α-Syn原纤维导致α-Syn组织病理学发展至中脑并随后发生运动缺陷。他们的研究结果描述了前驱性帕金森氏病周围突触核蛋白病理特征,并探索了α-Syn病理的肠道到大脑进展的细胞机制。

据介绍,帕金森氏病(PD)是一种突触核蛋白病,其特征是运动功能障碍,中脑多巴胺能神经元死亡和α-Syn聚集体聚集。

附:英文原文

Title: Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Author: Collin Challis, Acacia Hori, Timothy R. Sampson, Bryan B. Yoo, Rosemary C. Challis, Adam M. Hamilton, Sarkis K. Mazmanian, Laura A. Volpicelli-Daley, Viviana Gradinaru

Issue&Volume: 2020-02-17

Abstract: Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology.

DOI: 10.1038/s41593-020-0589-7

Source: https://www.nature.com/articles/s41593-020-0589-7

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新if:21.126
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex