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Does Parkinson’s disease start in the gut?
Acta Neuropathologica ( IF 9.3 ) Pub Date : 2017-10-16 , DOI: 10.1007/s00401-017-1777-8
Arthur Lionnet , Laurène Leclair-Visonneau , Michel Neunlist , Shigeo Murayama , Masaki Takao , Charles H. Adler , Pascal Derkinderen , Thomas G. Beach

Parkinson’s disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and coworkers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak’s hypothesis. This ‘gut to brain’ scenario has ignited heated debates within the movement disorders community and prompted a large number of studies in both humans and animals. Here, we review the arguments for and against the gut as the origin of PD. We conclude that the human autopsy evidence does not support the hypothesis and that it is too early to draw any definitive conclusions. We discuss how this issue might be further addressed in future research.



中文翻译:

帕金森氏病会从肠道开始吗?

帕金森氏病(PD)在病理学上的特征是存在神经内包涵体,称为路易体和路易神经突,其主要成分为α-突触核蛋白。根据对PD患者进行尸检后建立的路易体和神经突的地形分布,Braak及其同事推测,PD病理可能始于胃肠道,然后通过迷走神经扩散到大脑。通过发现α-突触核蛋白可能能够跨细胞扩散,从而为Braak的假说提供了机理基础,这一假设得到了进一步的证实。这种“直视大脑”的情况引发了运动障碍社区的激烈辩论,并引发了对人类和动物的大量研究。在这里,我们回顾支持和反对肠道作为PD起源的观点。我们得出的结论是,人体解剖学证据不支持该假设,并且得出任何明确的结论还为时过早。我们讨论了如何在将来的研究中进一步解决此问题。

更新日期:2017-10-16
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