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Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies

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...

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Autores principales: Kwon, Somin, Iba, Michiyo, Masliah, Eliezer, Kim, Changyoun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Brain and Neural Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844834/
https://www.ncbi.nlm.nih.gov/pubmed/31698547
http://dx.doi.org/10.5607/en.2019.28.5.547
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author Kwon, Somin
Iba, Michiyo
Masliah, Eliezer
Kim, Changyoun
author_facet Kwon, Somin
Iba, Michiyo
Masliah, Eliezer
Kim, Changyoun
author_sort Kwon, Somin
collection PubMed
description 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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spelling pubmed-68448342019-11-18 Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies Kwon, Somin Iba, Michiyo Masliah, Eliezer Kim, Changyoun Exp Neurobiol Review Article 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. The Korean Society for Brain and Neural Sciences 2019-10 2019-10-31 /pmc/articles/PMC6844834/ /pubmed/31698547 http://dx.doi.org/10.5607/en.2019.28.5.547 Text en Copyright © Experimental Neurobiology 2019 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Kwon, Somin
Iba, Michiyo
Masliah, Eliezer
Kim, Changyoun
Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title_full Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title_fullStr Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title_full_unstemmed Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title_short Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
title_sort targeting microglial and neuronal toll-like receptor 2 in synucleinopathies
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844834/
https://www.ncbi.nlm.nih.gov/pubmed/31698547
http://dx.doi.org/10.5607/en.2019.28.5.547
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