ArticleNature neuroscience2020
Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice.
Article in Nature neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
248 citing papers in PubMed, 4 syntheses or guidelines pooled it, 386 citations in OpenAlex.
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Experimental models of gut-first Parkinson's disease: A systematic review.Neurogastroenterology and motility · 2023Pooled it
- Impact of aging on animal models of Parkinson's disease.Frontiers in aging neuroscience · 2022Pooled it
- Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease.Frontiers in aging neuroscience · 2022Pooled it
- Gut microbiota modulation via repeated donor fecal transplantation improves motor and gastrointestinal symptoms in drug-naïve Parkinson's disease: a randomized phase 2 trial.Signal transduction and targeted therapy · 2026Trial
- Gut Microbiota Modulation in CNS Disorders: Therapeutic Strategies and Implications for Drug Efficacy.Molecular neurobiology · 2026Review
- The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Review
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Ingestible probes for breath-based monitoring of drug-metabolizing activity from the microbiome.Science advances · 2026Article
- Duodenal α-Synuclein PFF Injection Induces Vagus-Related Gut-to-Brain Pathology in C57BL/6J and A53T Transgenic Mice.Brain sciences · 2026Article
- Vagal neuropathies: An underrecognized potential driver of physical, mental, and immune symptoms.Brain, behavior, & immunity - health · 2026Review
- Emerging insight in genetics and therapies in young-onset Parkinson's disease (YOPD): a comprehensive review.Journal of neurology · 2026Review
- The Influence of Gut Microbiome on Alpha-Synuclein Aggregation: Implications for Parkinson's Disease Pathogenesis.Molecular neurobiology · 2026Review
- The Oral-Gut-Brain Axis: From Periodontal Dysbiosis to Neuroinflammation-Mechanistic Pathways, Salivary and Intestinal Biomarkers, and Therapeutic Targets: A Narrative Review.Dentistry journal · 2026Review
- Novel Insights Into the Association Between Parkinson's Disease and Constipation: Role of SHMT2 as a Promising Biomarker.CNS neuroscience & therapeutics · 2026Article
- Microbiota as a regulator of brain vulnerability across lifespan and disease contexts.Journal of neuroinflammation · 2026Review
- Consequences of Western and Mediterranean Diets' Nutrients on the Microbiota-Gut-Brain Axis.Nutrients · 2026Review
- Parkinson's disease: pathogenesis and therapeutic strategies.Molecular biomedicine · 2026Review
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
188 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Parkinson's disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson's disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.