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帕金森病中的肠道微生物代谢产物:线粒体功能障碍在发病机制和治疗中的意义。

Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment.

机构信息

Department of Neurology, First Hospital of Jilin University, Changchun, 130021, China.

Departments of Laboratory Medicine and Pathology, Neurology and Immunology, Mayo Clinic, Rochester, MN, USA.

出版信息

Mol Neurobiol. 2021 Aug;58(8):3745-3758. doi: 10.1007/s12035-021-02375-0. Epub 2021 Apr 6.

Abstract

The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.

摘要

帕金森病(PD)治疗靶点的寻找受到疾病病理生理学认识不完全的阻碍。线粒体功能障碍是一个具有高潜力的领域。肠道微生物组与中枢神经系统之间的神经生物学信号连接尚不完全清楚。多项证据表明,肠道微生物群参与 PD 的发病机制。肠道微生物失调可能通过线粒体功能障碍导致多巴胺能神经元丧失。通过微生物群-肠道-大脑轴干预肠道微生物代谢物可能成为 PD 的一种有前途的治疗策略。在这篇叙述性综述中,我们总结了肠道微生物失调在 PD 中的潜在作用,重点介绍了微生物代谢物和线粒体功能。然后,我们回顾了微生物代谢物影响中枢神经系统的可能途径,以及微生物代谢物对线粒体功能障碍的影响。最后,我们讨论了将肠道菌群作为 PD 治疗靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f7f/8280023/5f1253ea6ceb/12035_2021_2375_Fig1_HTML.jpg

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