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The Gut-Brain Axis: Two Ways Signaling in Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches.

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Acknowledgements

We acknowledge Dr. Ashok Chauhan, Founder, Amity University and honorable Chancellor Sir for providing us infrastructure and facilities and University Grant Commission (Government of India) for granting senior research fellowship to Ms Nitu Dogra to undertake this project.

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  1. Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Uttar Pradesh, Noida, 201313, India

    Nitu Dogra, Ruchi Jakhmola Mani & Deepshikha Pande Katare

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  1. Nitu Dogra
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  2. Ruchi Jakhmola Mani
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Dogra, N., Mani, R.J. & Katare, D.P. The Gut-Brain Axis: Two Ways Signaling in Parkinson’s Disease. Cell Mol Neurobiol 42, 315–332 (2022). https://doi.org/10.1007/s10571-021-01066-7

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