ArticleActa neuropathologica2017
Toll-like receptor 2 is increased in neurons in Parkinson's disease brain and may contribute to alpha-synuclein pathology.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 275 citations in OpenAlex.
- Association between TLR2 polymorphisms (- 196-174 Ins/Del, R677W, R753Q, and P631H) and schizophrenia in a Tunisian population.Immunologic research · 2021Trial
- 10,11-Dehydrocurvularin attenuates LPS-induced neuroinflammation in BV2 cells by inhibiting the TLR2/MyD88/NLRP3 signaling pathway.Biochemistry and biophysics reports · 2026Article
- Low-Dose Ionizing Radiation and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Review of Recent Evidence and Future Research Directions Toward the Elucidation of a Metabolic, Immunologic, and Signaling Cascade.International journal of molecular sciences · 2026Review
- APOE4-Expressing Astrocytes Exhibit Parkinson's Disease-Related Pathology.Molecular neurobiology · 2026Article
- Progress of Immunotherapies in Parkinson's Disease.CNS neuroscience & therapeutics · 2026Review
- Phloretin as a Multitarget Neuroprotective Agent: Mechanistic Insights into the Modulation of Oxidative Stress, Inflammation, and Apoptosis.Neuromolecular medicine · 2026Review
- Anti-TLR2 immunotherapy modulates neuron-to-oligodendrocyte propagation of α-synuclein in mouse and human models.Nature communications · 2026Article
- Diverse Effects of Various Toll-Like Receptor 2 Ligands on Neuronal Activity and Cell Death.Cellular and molecular neurobiology · 2025Article
- Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.Experimental & molecular medicine · 2025Article
- G protein-coupled Estrogen Receptor Activation Exerts Protective Effects via Modulating Brain and Gut NLRP3 Inflammasome in Parkinson's Disease.Experimental neurobiology · 2025Article
- Parkinson's disease: genetics and neuroinflammatory insights.Inflammopharmacology · 2025Review
- Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities.Nature communications · 2025Article
- Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- IGF2-Reprogrammed Macrophages Ameliorate the Inflammatory Response and Protect Against the Neuroinflammatory Process in Parkinson's Disease Models.Aging cell · 2025Article
- Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.Molecular neurodegeneration · 2025Review
- Positron emission tomography tracers for synucleinopathies.Molecular neurodegeneration · 2025Review
- Role of toll-like receptors in post-COVID-19 associated neurodegenerative disorders?Frontiers in medicine · 2025Review
- Sulfate reducing bacteria induce α-synuclein in intestinal and neuronal cells and tissues and inhibit tyrosine hydroxylase in neuronal cells.Frontiers in neuroscience · 2025Article
- Innate Immune Mechanisms in the Central Nervous System.Advances in experimental medicine and biology · 2025Review
- A Review of the Protective Effects of Alkaloids against Alpha-synuclein Toxicity in Parkinson's Disease.Mini reviews in medicinal chemistry · 2025Review
93 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Inflammation is likely a key contributor to the pathogenesis of Parkinson's disease (PD), a progressively debilitating neurodegenerative disease that is accompanied by a pathological accumulation of the α-synuclein protein in a staged manner through the brain. What leads to the accumulation of α-synuclein in PD and how this relates to inflammatory pathways, however, is not entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation and, in particular, TLR2 is increasingly being implicated in PD. We have, therefore, examined the expression of TLR2 in postmortem brain tissue from PD patients and matched controls. We confirm that TLR2 is increased in PD brain, and find that levels of TLR2 correlate with the accumulation of pathological α-synuclein. TLR2 was expressed on neurons as well as microglia; however, the neuronal rather than glial expression of TLR2 was significantly increased in PD brain in accordance with disease staging, and TLR2 was strongly localized to α-synuclein positive Lewy bodies. In cell culture, activation of neuronal TLR2 induced an inflammatory response, including the secretion of inflammatory cytokines and microglial-activating chemokines, as well as the production of reactive oxygen species. Moreover, activation of neuronal TLR2 increased levels of endogenous α-synuclein protein, which was in turn associated with increased levels of the autophagy/lysosomal pathway marker p62. Finally, promoting autophagy with rapamycin or pharmacological inhibition of the TLR2 signaling pathway prevented the TLR2-mediated increase in α-synuclein in neuronal cell cultures. These results implicate neuronal TLR2 expression in human PD pathogenesis. In particular, the increased expression of TLR2 on neurons may provide new insight into disease pathogenesis and/or options for therapeutic intervention.
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