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

Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies

• Kwon S
• Iba M
• Masliah E
• Kim C

• KMID: 2463710
• DOI: http://doi.org/10.5607/en.2019.28.5.547

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.

Keyword

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

MeSH Terms

Animals
Autophagy
Dementia
Immunotherapy
Lewy Bodies
Mice
Neurodegenerative Diseases
Neuroglia
Neurons*
Neuropathology
Parkinson Disease
Toll-Like Receptor 2*
Toll-Like Receptors*
Toll-Like Receptor 2
Toll-Like Receptors