Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice
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Pathological studies on Parkinson's disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PD.
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Progression of pathologically expressed alpha-synuclein towards the brain could be halted by resection of sympathetic and parasympathetic nerves prior to oral rotenone treatment.
“Two years later, the same research group showed that the progression of pathologically expressed alphasynuclein towards the brain could be halted by the resection of sympathetic and parasympathetic nerves prior to oral rotenone treatment (Pan-Montojo et al., 2012).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Pan-Montojo et al., 2012
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“Two years later, the same research group showed that the progression of pathologically expressed alphasynuclein towards the brain could be halted by the resection of sympathetic and parasympathetic nerves prior to oral rotenone treatment (Pan-Montojo et al., 2012).”
BackgroundThe Threshold Theory for Parkinson's Disease
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- Authors
- Pan-Montojo, F., Schwarz, M., Winkler, C., Arnhold, M., O'Sullivan, G. A., Pal, A., Said, J., Marsico, G., Verbavatz, J.-M., Rodrigo-Angulo, M., Gille, G., Funk, R. H. W., & Reichmann, H.
- Affiliations
- Technische Universität Dresden (DE)
- University Hospital Carl Gustav Carus (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Center for Regenerative Therapies Dresden (DE)
- Corresponding author
- Pan-Montojo, Francisco
- ORCID
- Venue
- Scientific Reports
- Published
- 2012-11-30
- Volume
- 2
- Issue
- 1
- Pages
- 898-898
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3510466
- OpenAlex
- W2033185924
- Cited by
- 405
- References
- 47
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 18 · 2023: 23 · 2022: 41 · 2021: 32 · 2020: 52 · 2019: 37 · 2018: 30 · 2017: 45 · 2016: 26 · 2015: 26 · 2014: 26 · 2013: 25 · 2012: 1
- FWCI
- 16.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, cc-by-nc-nd)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Hispana (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, cc-by-nc-nd)
- Funders
- Parkinson's UK
- 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 › Physiology › Alzheimer's disease research and treatments
- Keywords
- Parkinson's disease, alpha-synuclein, enteric nervous system, environmental toxins, rotenone, pesticide exposure, transneuronal spread, retrograde axonal transport, enteric neurons, disease progression
- MeSH terms
- Animals, Axonal Transport, Brain, Humans, Insecticides, Neurons, Parkinson Disease, Secondary, Rotenone, Sympathectomy, Vagotomy, Enteric Nervous System, Mice, alpha-Synuclein, Primary Cell Culture
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