Format

Send to

Choose Destination
Exp Neurobiol. 2019 Oct 31;28(5):547-553. doi: 10.5607/en.2019.28.5.547.

Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies.

Author information

1
Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.

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.

KEYWORDS:

Immunotherapy; Neuroinflammation; Synucleinopathy; Toll-like receptor 2; α-synuclein

Supplemental Content

Full text links

Icon for The Korean Society for Brain and Neural Science Icon for PubMed Central
Loading ...
Support Center