基于肠脑轴传播α-突触核蛋白诱发帕金森病的研究进展

Advances in Parkinson's disease induced by α-synuclein transmitted through the gut-brain axis

摘要:

帕金森病（Parkinson’s disease，PD）是最常见的神经退行性疾病，随着我国人口老龄化加剧，PD病人的增加将造成严重的经济和医疗负担。PD的典型病理特征是黑质致密部多巴胺能神经元的死亡以及多巴胺能神经元中异常聚集的淀粉样蛋白α-突触核蛋白（α-synuclein，α-Syn）形成病理包涵体即路易小体（Lewy body）。研究发现路易小体不仅存在中枢神经系统中，也同样存在于外周神经系统。肠道内丰富的肠神经系统被称为“第二大脑”。肠脑轴的发现也证明α-Syn能在大脑和肠道进行双向传输。肠道中也存在着庞大的微生物群，这些微生物参与病理性α-Syn的形成和传输。因此文中基于肠脑轴探讨α-Syn在大脑和肠道的双向传输关系，尝试探索肠道微生物群对α-Syn异常聚集的影响。结合目前PD病人的研究和动物模型尤其是非人灵长类实验的研究，希望为PD疾病的筛查和诊断提供参考。

关键词:帕金森病;α-突触核蛋白;肠脑轴;肠道微生物;动物模型

Abstract:

Parkinson's disease (PD) is the most common neurodegenerative disease. Along with the population aging of China, the increase of PD patients in China will result in serious economic and medical burdens. The typical pathological characteristics of PD are the death of dopaminergic neurons in the substantia nigra compacta and the pathological inclusion bodies formed by abnormally aggregated amyloid alpha-synuclein (α-Syn) in dopaminergic neurons, which is also named as Lewy body. Studies have found that the Lewy body exists not only in the central nervous system, but also in the peripheral nervous system. The abundant enteric nervous system in the gut is called the "second brain". The discovery of the gut-brain axis also proves that α-Syn can be transmitted bilaterally between the brain and the gut. The gut microbiota was shown to be involved in the formation and transmission of pathological α-Syn. Therefore, this article summarized the bilateral transmission relationship of α-Syn in the brain and the gut and illustrated the influence of gut microbiota on the abnormal aggregation of α-Syn. Combined with the current progresses on PD patients and animal models especially the non-human primate experiments, this article aimed to provide a reference for the screening and diagnosis of PD.

Key words:Parkinson's disease;α-synuclein;gut-brain axis;gut microbes;animal model