ArticleNPJ Parkinson's disease2022
Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson's disease before brain pathology.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Experimental models of gut-first Parkinson's disease: A systematic review.Neurogastroenterology and motility · 2023Pooled it
- TLR2 Regulates α-Synuclein Phosphorylation and Release in an Enteroendocrine Cell Model.Molecular neurobiology · 2026Article
- Preventive Attenuation of MPTP-Induced Parkinson's Disease-like Abnormalities byFoods (Basel, Switzerland) · 2026Article
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Bile Acid Dysregulation in Parkinson's Disease: Longitudinal Changes and Altered Metabolic Interactions.Biomolecules · 2026Article
- TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation.Nature communications · 2026Article
- Early intestinal barrier changes in A53T transgenic Parkinson's disease mice.Cell and tissue research · 2026Article
- Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- enGLOW 3D microscopy of the enteric nervous system in cleared human and mouse gut.Communications biology · 2026Article
- Enteric glia, neuropeptides, and Parkinson's: impacts of calcitonin gene-related peptide on gut alpha synuclein.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Highly sensitive chemiluminescence imaging of misfolded proteins in neurodegenerative models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Examination of shared gut microbiome signatures in aging and Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- G protein-coupled Estrogen Receptor Activation Exerts Protective Effects via Modulating Brain and Gut NLRP3 Inflammasome in Parkinson's Disease.Experimental neurobiology · 2025Article
- Recent Insights About Probiotics Related Pharmabiotics in Pharmacology: Prevention and Management of Diseases.Probiotics and antimicrobial proteins · 2025Review
- Integrative systems biology approaches for analyzing microbiome dysbiosis and species interactions.Briefings in bioinformatics · 2025Review
- The interrelationship between intestinal immune cells and enteric α-synuclein in the progression of Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- α-Synuclein in Parkinson's Disease: From Bench to Bedside.Medicinal research reviews · 2025Review
- Review
- Research progress on natural products in regulating the gut microbiota in Parkinson's disease.Frontiers in pharmacology · 2025Review
- Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet-induced obesity.Acta physiologica (Oxford, England) · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1β, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1β release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central 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.