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Review Article

Exp Neurobiol 2019; 28(5): 547-553

Published online October 31, 2019

© The Korean Society for Brain and Neural Sciences

Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies

Somin Kwon, Michiyo Iba, Eliezer Masliah and Changyoun Kim*

Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA

Correspondence to: *To whom correspondence should be addressed.
TEL: 1-301-451-2120, FAX: 1-301-451-7295

Received: August 28, 2019; Revised: September 19, 2019; Accepted: October 4, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License( which permits unrestricted non-commercial use, distribution, andreproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Neuroinflammation, &alpha,-synuclein, Toll-like receptor 2, Immunotherapy, Synucleinopathy