ArticleNeuron2019
Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease.
2 registry-linked trialsOpen access · bronzeAbstract readVideo-Audio Media
In one paragraph
Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 824 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
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824citing papers in PubMed, 6 pooled it
106.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Role and Mechanism of Bifidobacterium Triple Viable Capsules in Improving Motor Symptoms in Patients With Mild to Moderate Parkinson's Disease: a Multicenter Randomized Clinical Study
Fecal Microbiota Transplantation for the Treatment of Patients With Parkinson's Disease.
Who cites it
824 citing papers in PubMed, 6 syntheses or guidelines pooled it, 1,324 citations in OpenAlex.
- Efficacy and safety of fecal microbiota transplantation in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Ultrasonography demonstrates vagus nerve atrophy in Parkinson's disease: a meta-analysis.Journal of neurology · 2026Pooled it
- Enteric Nervous System Damage by Food Contaminants: A Pathway to Neurodegeneration?Comprehensive reviews in food science and food safety · 2026Pooled it
- Gut-brain axis dysfunction in Parkinson's disease: a meta-analysis of microbiome dysbiosis and intestinal barrier markers.Frontiers in medicine · 2026Pooled it
- Global research trends in enteric nervous system and gut microbiota: a bibliometric analysis (2005-2025).Frontiers in cellular and infection microbiology · 2026Pooled it
- The role of the gut microbiome in the progression of Parkinson's disease: a systematic review of patient cohorts.Journal of neurology · 2025Pooled 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
- Effect of Probiotics Supplementation on REM Sleep Behavior Disorder and Motor Symptoms in Parkinson's Disease: A Pilot Study.CNS neuroscience & therapeutics · 2025Trial
- Research advances in the microbiota‑gut‑brain axis and Parkinson's disease (Review).Molecular medicine reports · 2026Review
- Normative Modeling of Amygdala Subfields and Disease-Specific Vulnerabilities Across Neurological Disorders.Neuroscience bulletin · 2026Article
- Fecal Microbiota Transplantation BeyondJournal of Korean medical science · 2026Review
- The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Review
- Review
- TLR2 Regulates α-Synuclein Phosphorylation and Release in an Enteroendocrine Cell Model.Molecular neurobiology · 2026Article
- Sleep Disorders in Neurodegenerative Diseases: Pathological Correlations and Underlying Mechanisms.Neuroscience bulletin · 2026Review
- The Gut-Brain Axis in Neurodegeneration: Mechanistic Links Between Dysbiosis and Neuropathology.Iranian journal of pathology · 2026Review
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- The Gut-Brain Axis: A Critical Link between Type 2 Diabetes and Parkinson's disease.Probiotics and antimicrobial proteins · 2026Review
764 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Sangjune KimNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Seung-Hwan KwonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Tae-In KamNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nikhil PanickerNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Senthilkumar S KaruppagounderNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Saebom LeeNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jun Hee LeeNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Wonjoong Richard KimNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Minjee KookNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Catherine A FossThe Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chentian ShenThe Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hojae LeeNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Subhash KulkarniCenter for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Pankaj J PasrichaCenter for Neurogastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gabsang LeeNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Martin G PomperThe Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: tdawson@jhmi.edu.
Han Seok KoNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: hko3@jhmi.edu.
Johns Hopkins University · US
Funding
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8MThe role of NOD2/RIPK2 signaling in the pathogenesis of Parkinson's DiseaseR01NS107404 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 2018 to 2022
$1.8MGlucocerebrosidase Biology and It's Role in Parkinson's DiseaseR01NS082205 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 2013 to 2017
$1.8MCharacterization and Validation of Mouse VPS35 Model of Parkinson's DiseaseR21NS098006 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 2017 to 2018
$449kNINDS NIH HHS P50 NS038377NINDS NIH HHS R01 NS082205NINDS NIH HHS R01 NS107404NINDS NIH HHS R21 NS098006
Abstract
Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson's disease (PD).
Indexed as
Axonal TransportProtein Aggregatesalpha-SynucleinAnimalsBrain ChemistryDopaminergic NeuronsDuodenumHumansInjections, IntramuscularLewy BodiesMaze LearningMemory DisordersMiceMice, Inbred C57BLMice, KnockoutModels, Neurologicalalpha-SynucleinProtein AggregatesSnca protein, mouseBraak hypothesisgut to brain transmissionLewy body pathologymotor symptomsneurodegenerationnon-motor symptomsParkinson’s diseasepre-formed fibrilsvagus nerveα-synuclein
Identifiers
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Registered trials
NCT04871464ClinicalTrials.gov
NCT07597421ClinicalTrials.gov
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.