Gut–brain axis and the spread of α‐synuclein pathology: Vagal highway or dead end?
Abstract
Spread of α-synuclein pathology from the peripheral to central nervous system may be an important etiological factor in Parkinson's disease, although there are some unanswered questions about its correlation with neuronal loss. Experimental evidence has highlighted the gastrointestinal tract as a potential starting point for aggregated α-synuclein, with the vagus nerve acting as a "highway" by which pathology may be transmitted to the lower brain stem. This review begins by highlighting the key studies demonstrating that α-synuclein pathology has the ability to spread from certain sites in the gastrointestinal tract to the brain (and vice versa). We go on to assess the recent epidemiological studies that have shown that vagotomy and appendectomy may have the potential to reduce the risk of developing Parkinson's disease. Finally, we discuss the factors in the gastrointestinal tract (such as dysbiosis of the gut microbiota, infection, and inflammation) that may trigger α-synuclein aggregation in the first place, as well as other potential mechanisms underlying the distribution of α-synuclein pathology in the brain. © 2019 International Parkinson and Movement Disorder Society.
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Prion-like propagation model suggests that α-synuclein is transported intra-axonally, released into the extracellular space, taken up by neighboring neurons, where it seeds aggregation and endogenous α-synuclein synthesis inside the next cell.
“One leading and provocative model suggests that it occurs through prion-like propagation: α-synuclein is transported intra-axonally, released into the extracellular space, taken up by neighboring neurons, where it seeds aggregation and endogenous α-synuclein synthesis inside the next cell [54, 78].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [54]
Retrograde spread of α-synuclein pathology from a gastric source to the DMV is thought to involve the vagus nerve.
“Retrograde spread of α-synuclein pathology from a gastric source to the DMV is thought to involve the vagus nerve [54, 55].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [54]
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- Authors
- Breen, D. P., Halliday, G. M., & Lang, A. E.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- The University of Sydney (AU)
- Toronto Western Hospital (CA)
- Corresponding author
- Breen, David P.
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2019-01-17
- Volume
- 34
- Issue
- 3
- Pages
- 307-316
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- OpenAlex
- W2909716959
- Cited by
- 193
- References
- 13
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 19 · 2023: 23 · 2022: 36 · 2021: 28 · 2020: 36 · 2019: 23
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- gut-brain axis, alpha-synuclein pathology, Parkinson's disease, vagus nerve, vagotomy, appendectomy, gut dysbiosis, gastrointestinal infections, neuroinflammation, alpha-synuclein aggregation
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Humans, Parkinson Disease, Vagus Nerve, Gastrointestinal Tract, alpha-Synuclein
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