Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies
Experimental Neurobiology
;
: 547-553, 2019.
Article
in English
| WPRIM
| ID: wpr-763791
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Parkinson Disease
/
Autophagy
/
Neuroglia
/
Lewy Bodies
/
Neurodegenerative Diseases
/
Dementia
/
Toll-Like Receptors
/
Toll-Like Receptor 2
/
Neuropathology
/
Immunotherapy
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental Neurobiology
Year:
2019
Type:
Article
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