ArticleCell death discovery2021
Phosphorylated α-synuclein aggregated in Schwann cells exacerbates peripheral neuroinflammation and nerve dysfunction in Parkinson's disease through TLR2/NF-κB pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Gasdermin D in Neurodegenerative Diseases: Pathogenic Roles and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- The complement C3-microglial axis in depression of Parkinson's disease: from mechanism to therapeutic intervention.EBioMedicine · 2026Article
- Cross-Linking and Covalent Labeling Mass Spectrometry Reveal Proteoform-Driven Conformational Changes in Alpha Synuclein.Analytical chemistry · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 2025Review
- Self-reported autonomic dysfunction could be a predictive marker for sarcopenia in Parkinson's disease.Geriatrics & gerontology international · 2025Article
- Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.Molecular neurobiology · 2025Review
- Experimental Evidence for Phosphorylation-Driven Allosteric Regulation of Alpha Synuclein Function.bioRxiv : the preprint server for biology · 2025Article
- Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration.Journal of molecular neuroscience : MN · 2024Review
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson's disease autonomic dysfunction.Cell death discovery · 2024Article
- Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding.Frontiers in molecular neuroscience · 2024Review
- Involvement of Abnormal p-α-syn Accumulation and TLR2-Mediated Inflammation of Schwann Cells in Enteric Autonomic Nerve Dysfunction of Parkinson's Disease: an Animal Model Study.Molecular neurobiology · 2023Article
- Role of neuroinflammation in neurodegeneration development.Signal transduction and targeted therapy · 2023Review
- Alpha Synuclein: Neurodegeneration and Inflammation.International journal of molecular sciences · 2023Review
- α-Synuclein induces prodromal symptoms of Parkinson's disease via activating TLR2/MyD88/NF-κB pathway in Schwann cells of vagus nerve in a rat model.Journal of neuroinflammation · 2023Article
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
To investigate the mechanism of peripheral neuropathy in Parkinson's disease (PD), we prepared a PD mice model by long-term exposure of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mimic PD pathology in humans and the sciatic nerves were taken for further research. It turned out that phosphorylated α-synuclein (p-α-syn) was significantly deposited in Schwann cells (SCs) of sciatic nerves possibly contributing to degenerated myelin SCs and atrophied axons in MPTP group. Further analysis confirmed that toll-like receptors (TLRs) were implicated with PD peripheral neuropathy, in which TLR2 exhibits the predominant expression. Increased expression of inflammatory factors about TLR2/nuclear factor kappa-B (NF-κB) pathway was noted in MPTP group compared to saline group, with proteins on other pathways showing no changes. Moreover, MPTP-challenged mice exhibited worse motor ability and damaged nerve conduction, implicating that p-α-syn neurotoxicity might be relevant to impairments of motor and sensory nerves. After the treatment of CU-CPT22, a TLR2 antagonist, p-α-syn accumulation, motor and sensory function were ameliorated in CU-CPT22 combined with MPTP group. Thus, we demonstrated that pathological p-α-syn might combine TLR2 to affect SCs activation, inflammatory response as well as motor and sensory function through TLR2/nuclear factor kappa-B (NF-κB) signaling pathway. This study firstly demonstrates a novel mechanism of p-α-syn accumulated in SCs of peripheral nerves, which extends our understanding on SCs-mediated peripheral neuroinflammation related to TLR2/NF-κB signaling pathway and sheds light on potential new therapeutic avenues for PD.
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What OpenQuestion holds
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.