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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Society for Brain and Neural Sciences
2019
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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. |
format | Online Article Text |
id | pubmed-6844834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Korean Society for Brain and Neural Sciences |
record_format | MEDLINE/PubMed |
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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