ArticleExperimental neurobiology2016
Non-cell-autonomous Neurotoxicity of α-synuclein Through Microglial Toll-like Receptor 2.
Article in Experimental neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 91 citations in OpenAlex.
- Differential microglial responses to structurally distinct alpha-synuclein polymorphs.Molecular brain · 2025Article
- Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.Experimental & molecular medicine · 2025Article
- The Neurotoxic Properties of α-synuclein Polymorphs.Experimental neurobiology · 2025Article
- Microglia-driven inflammation induces progressive tauopathies and synucleinopathies.Experimental & molecular medicine · 2025Article
- Long-Term Engraftment of Cryopreserved Human Neurons for In Vivo Disease Modeling in Neurodegenerative Disease.Biology · 2025Article
- Deciphering motor dysfunction and microglial activation in mThy1-Frontiers in molecular neuroscience · 2025Article
- Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson's disease overexpressing human alpha synuclein.NPJ Parkinson's disease · 2024Article
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Basal forebrain integrity, cholinergic innervation and cognition in idiopathic Parkinson's disease.Brain : a journal of neurology · 2024Article
- Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Microglial inhibition alleviates alpha-synuclein propagation and neurodegeneration in Parkinson's disease mouse model.NPJ Parkinson's disease · 2024Article
- The Role of Immune Dysfunction in Parkinson's Disease Development.International journal of molecular sciences · 2023Review
- Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review.International journal of molecular sciences · 2023Article
- Role of neuroinflammation in neurodegeneration development.Signal transduction and targeted therapy · 2023Review
- Pathophysiology and Neuroimmune Interactions Underlying Parkinson's Disease and Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- A functional role for alpha-synuclein in neuroimmune responses.Journal of neuroimmunology · 2023Review
- Host immune responses in the central nervous system during fungal infections.Immunological reviews · 2022Review
- Role of exosomes in the pathogenesis of inflammation in Parkinson's disease.Neural regeneration research · 2022Review
- Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson's Disease.International journal of molecular sciences · 2022Article
- The role of Toll-like receptors and neuroinflammation in Parkinson's disease.Journal of neuroinflammation · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Synucleinopathies are a collection of neurological diseases that are characterized by deposition of α-synuclein aggregates in neurons and glia. These diseases include Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. Although it has been increasingly clear that α-synuclein is implicated in the pathogenesis of PD and other synucleinopathies, the precise mechanism underlying the disease process remains to be unraveled. The past studies on how α-synuclein exerts pathogenic actions have focused on its direct, cell-autonomous neurotoxic effects. However, recent findings suggested that there might be indirect, non-cell-autonomous pathways, perhaps through the changes in glial cells, for the pathogenic actions of this protein. Here, we present evidence that α-synuclein can cause neurodegeneration through a non-cell-autonomous manner. We show that α-synuclein can be secreted from neurons and induces inflammatory responses in microglia, which in turn secreted neurotoxic agents into the media causing neurodegeneration. The neurotoxic response of microglia was mediated by activation of toll-like receptor 2 (TLR2), a receptor for neuron-derived α-synuclein. This work suggests that TLR2 is the key molecule that mediates non-cell-autonomous neurotoxic effects of α-synuclein, hence a candidate for the therapeutic target.
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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.