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Cited by 35Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies

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Kwon, Somin, Iba, Michiyo, Masliah, Eliezer, Kim, Changyoun·2019·Experimental Neurobiology
DOI 10.5607/en.2019.28.5.547PMC PMC6844834
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Abstract

Synucleinopathies are neurodegenerative disorders characterized by the progressive accumulation of α-synuclein (α-syn) in neurons and glia and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this review, we consolidate our key findings and recent studies concerning the role of Toll-like receptor 2 (TLR2), a pattern recognition innate immune receptor, in the pathogenesis of synucleinopathies. First, we address the pathological interaction of α-syn with microglial TLR2 and its neurotoxic inflammatory effects. Then, we show that neuronal TLR2 activation not only induces abnormal α-syn accumulation by impairing autophagy, but also modulates α-syn transmission. Finally, we demonstrate that administration of a TLR2 functional inhibitor improves the neuropathology and behavioral deficits of a synucleinopathy mouse model. Altogether, we present TLR2 modulation as a promising immunotherapy for synucleinopathies.

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  • Neuron-released α-synuclein induces neurotoxic, pro-inflammatory microglial responses through Toll-like receptor 2 (TLR2).

    “Neuron-released α-synuclein has been shown to induce neurotoxic, pro-inflammatory microglial responses through Toll-like receptor 2 (TLR2) but the molecular mechanisms involved are poorly understood.”

    From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [9]

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Cited by

Sorted by citations

Authors
Kwon, S., Iba, M., Masliah, E., & Kim, C.
Affiliations
National Institutes of Health (US)
Corresponding author
Kim, Changyoun
ORCID
Venue
Experimental Neurobiology
Publisher
The Korean Society for Brain and Neural Science
Published
2019-10-31
Volume
28
Issue
5
Pages
547-553
ISSN
  • 1226-2560 (ISSN-L)
  • 2093-8144
DOI
10.5607/en.2019.28.5.547
PMC
PMC6844834
OpenAlex
W2984206771
Cited by
35
References
10
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 9 · 2021: 3 · 2020: 10
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Experimental Neurobiology (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institutes of Health, National institute on Aging
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
TLR2, synucleinopathies, alpha-synuclein, Parkinson's disease, dementia with Lewy bodies, microglia, innate immunity, neuroinflammation, autophagy, immunotherapy, neurodegeneration

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