Work

Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies

Year: 2019

Type: review

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.

Source: Experimental Neurobiology

DOI: 10.5607/en.2019.28.5.547

Authors: Somin Kwon, Michiyo Iba, Eliezer Masliah, Changyoun Kim

Institutions: National Institutes of Health, National Institute on Aging

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Institutes of Health