The Gut-Brain Axis Based on α-Synuclein Propagation-Clinical, Neuropathological, and Experimental Evidence
Ryosuke Takahashi1, Hodaka Yamakado2, Norihito Uemura3
1Kyoto University Office of Research Acceleration, Kyoto 606-8501, Japan.
International Journal of Molecular Sciences
|May 14, 2025
Summary
Parkinson's disease (PD) pathology may originate in the gut. Alpha-synuclein (aSyn) aggregates in the enteric nervous system (ENS) and potentially spreads to the brain, contributing to PD progression.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Parkinson's disease (PD) is characterized by Lewy bodies (LBs), primarily composed of alpha-synuclein (aSyn).
- ASyn is known to propagate between neurons, suggesting a mechanism for PD pathology spread.
- Initial LB pathology is observed in the dorsal motor nucleus of the vagus (DMV) or olfactory bulb.
Purpose of the Study:
- To review evidence for or against the hypothesis that aSyn propagation from the enteric nervous system (ENS) to the brain causes PD.
- To discuss alternative mechanisms of aSyn spreading, such as through systemic circulation or multifocal generation.
Main Methods:
- Review of clinical evidence.
- Review of neuropathological studies.
- Review of experimental findings.
Main Results:
- The ENS innervates the DMV, and LBs are found in the gut's nerve plexuses, supporting the gut-to-brain propagation theory.
- Evidence is presented for and against the ENS as the origin of PD pathology.
- Alternative theories of aSyn spreading are considered.
Conclusions:
- The gut-to-brain axis is a plausible route for aSyn propagation in PD.
- Further research is needed to elucidate the precise mechanisms and origins of aSyn spreading in PD.
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