Department of Neurology, CHU Nantes, 44093, Nantes, France.
Inserm, U1235, 1, rue Gaston Veil, 44035, Nantes Cedex 1, France.
Acta Neuropathol. 2018 Jan;135(1):1-12. doi: 10.1007/s00401-017-1777-8. Epub 2017 Oct 16.
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.
帕金森病（PD）的病理学特征为存在神经元内包涵体，称为路易体和路易神经突，其主要成分是α-突触核蛋白。基于尸检后从 PD 患者中建立的路易体和神经突的拓扑分布，Braak 及其同事假设 PD 病理学可能始于胃肠道，然后通过迷走神经传播到大脑。这一假设得到了进一步的支持，即α-突触核蛋白可能具有跨细胞传播的能力，从而为 Braak 的假设提供了机制基础。这种“肠道到大脑”的情景在运动障碍领域引发了激烈的争论，并促使人们在人类和动物中进行了大量研究。在这里，我们回顾了支持和反对肠道作为 PD 起源的论点。我们的结论是，人体尸检证据并不支持这一假设，现在下任何明确的结论还为时过早。我们讨论了如何在未来的研究中进一步解决这个问题。
