The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease
Open accessAbstract
Parkinson’s disease (PD) is a progressive neurodegenerative disease with devastating clinical manifestations. In PD, neuronal death is associated with intracellular aggregates of the neuronal protein α-synuclein known as Lewy bodies. Although the cause of sporadic PD is not well understood, abundant clinical and pathological evidence show that misfolded α-synuclein is found in enteric nerves before it appears in the brain. This suggests a model in which PD pathology originates in the gut and spreads to the central nervous system via cell-to-cell prion-like propagation, such that transfer of misfolded α-synuclein initiates misfolding of native α-synuclein in recipient cells. We recently discovered that enteroendocrine cells (EECs), which are part of the gut epithelium and directly face the gut lumen, also possess many neuron-like properties and connect to enteric nerves. In this report, we demonstrate that α-synuclein is expressed in the EEC line, STC-1, and native EECs of mouse and human intestine. Furthermore, α-synuclein–containing EECs directly connect to α-synuclein–containing nerves, forming a neural circuit between the gut and the nervous system in which toxins or other environmental influences in the gut lumen could affect α-synuclein folding in the EECs, thereby beginning a process by which misfolded α-synuclein could propagate from the gut epithelium to the brain.
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“Both cell types naturally express α-synuclein and offer a theoretical source for early pathological α-synuclein aggregation and spread to the brain via the vagus nerve [9, 137].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [137]
In the citing paper
“Gastrointestinal enteroendocrine cells that connect directly to the gut lumen and local neurones, and submucosal neurones which synapse micrometers from the gut lumen, could also be sources of α-synuclein [137].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [137]
In the citing paper
“Both cell types naturally express α-synuclein and offer a theoretical source for early pathological α-synuclein aggregation and spread to the brain via the vagus nerve [9, 137].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [137]
Citations
Cites
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Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
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Gut microbiota are related to Parkinson's disease and clinical phenotype
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Rotenone, Paraquat, and Parkinson’s Disease
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Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
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Colonic bacterial composition in Parkinson's disease
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Cited by
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Kim, S., Kwon, S.-H., Kam, T.-I., Panicker, N., Karuppagounder, S. S., Lee, S., Lee, J. H., Kim, W. R., Kook, M., Foss, C. A., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.035 · Cited by 1,397
Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Parker, A., Fonseca, S., & Carding, S. R. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1638722 · Cited by 745
Maiti, P., Manna, J., & Dunbar, G. L. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0099-z · Cited by 557
The gut microbiota and healthy aging: A mini-review
Kim, S., & Jazwinski, S. M. (2018) · Gerontology · doi:10.1159/000490615 · Cited by 427
Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice
Challis, C., Hori, A., Sampson, T. R., Yoo, B. B., Challis, R. C., Hamilton, A. M., Mazmanian, S. K., Volpicelli-Daley, L. A., & Gradinaru, V. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0589-7 · Cited by 405
Metadata
- Authors
- Chandra, R., Hiniker, A., Kuo, Y.-M., Nussbaum, R. L., & Liddle, R. A.
- Affiliations
- Duke University (US)
- Department of Pathology and
- University of California, San Francisco (US)
- Venue
- JCI Insight
- Published
- 2017-06-15
- Volume
- 2
- Issue
- 12
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5470880
- OpenAlex
- W2626849072
- Cited by
- 236
- References
- 67
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 28 · 2023: 26 · 2022: 43 · 2021: 28 · 2020: 15 · 2019: 20 · 2018: 23 · 2017: 4
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (BX002230, I01 BX002230)
- Sandler Foundation
- National Institutes of Health (UL1TR001117)
- University of California, San Francisco
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK098796, R01DK109368)
- National Institute of Neurological Disorders and Stroke (K08NS090633)
- Duke Cancer Institute
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, Parkinson's disease, enteroendocrine cells, gut-brain axis, Lewy bodies, prion-like propagation, enteric nerves, STC-1 cells, neurodegeneration, intestinal epithelium
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