Open Access

Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review)

  • Authors:
    • Qingchun Lei
    • Tingting Wu
    • Jin Wu
    • Xiaogang Hu
    • Yingxia Guan
    • Ying Wang
    • Jinyuan Yan
    • Guolin Shi
  • View Affiliations

  • Published online on: August 16, 2021     https://doi.org/10.3892/mmr.2021.12374
  • Article Number: 734
  • Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle‑aged and elderly populations. Several studies have confirmed that the microbiota‑gut‑brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α‑synuclein (α‑syn) in the intestine. Abnormal α‑syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α‑syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α‑syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α‑syn in the intestine caused by the GM changes and the increased levels of α‑syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α‑syn accumulation to relieve the symptoms and progression of PD are described.
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October-2021
Volume 24 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lei Q, Wu T, Wu J, Hu X, Guan Y, Wang Y, Yan J and Shi G: Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review). Mol Med Rep 24: 734, 2021
APA
Lei, Q., Wu, T., Wu, J., Hu, X., Guan, Y., Wang, Y. ... Shi, G. (2021). Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review). Molecular Medicine Reports, 24, 734. https://doi.org/10.3892/mmr.2021.12374
MLA
Lei, Q., Wu, T., Wu, J., Hu, X., Guan, Y., Wang, Y., Yan, J., Shi, G."Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review)". Molecular Medicine Reports 24.4 (2021): 734.
Chicago
Lei, Q., Wu, T., Wu, J., Hu, X., Guan, Y., Wang, Y., Yan, J., Shi, G."Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review)". Molecular Medicine Reports 24, no. 4 (2021): 734. https://doi.org/10.3892/mmr.2021.12374