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KMID : 0892920190280050547
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Experimental Neurobiology
2019 Volume.28 No. 5 p.547 ~ p.553
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Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
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Kwon So-Min
Iba Michiyo
Masliah Eliezer
Kim Chang-Youn
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Abstract
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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.
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KEYWORD
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Neuroinflammation, α-synuclein, Toll-like receptor 2, Immunotherapy, Synucleinopathy
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