Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
- Author:
Somin KWON
1
;
Michiyo IBA
;
Eliezer MASLIAH
;
Changyoun KIM
Author Information
- Publication Type:Review
- Keywords: Neuroinflammation; α-synuclein; Toll-like receptor 2; Immunotherapy; Synucleinopathy
- MeSH: Animals; Autophagy; Dementia; Immunotherapy; Lewy Bodies; Mice; Neurodegenerative Diseases; Neuroglia; Neurons; Neuropathology; Parkinson Disease; Toll-Like Receptor 2; Toll-Like Receptors
- From:Experimental Neurobiology 2019;28(5):547-553
- CountryRepublic of Korea
- Language:English
- 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.
