Roles of FcγRIIb signaling pathways in the pathogenesis of Parkinson’s disease

일반대학원 의생명과학과
The Graduate School, Ajou University
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Alternative Abstract
α-Synuclein (α-Syn) has been considered to be a key player of the pathogenesis of PD, and recent reports that prion-like propagation of misfolded α-syn released from neurons may play an important role in the progression of PD have led to increased attention to the studies elucidating the roles of extracellular α-syn in the CNS. Extracellular α-syn has also been reported to regulate microglial inflammatory response including phagocytosis. Here, I demonstrate that how α-syn fibrils inhibits microglial phagocytosis to take advantage of immune complexes-induced phagocytosis model. α-syn fibrils bound to FcγRIIB on microglia, inducing SHP-1 activation, further inhibiting microglial phagocytosis. Further, I show that FcγRIIB expressed in neurons functions as a receptor for α-syn fibrils and mediates cell-to-cell transmission of α-syn. SHP-1 /-2 and c-Src are activated downstream by α-syn fibrils through FcγRIIB and play an important role in cell-to-cell transmission of α-syn. Also, taking advantage of a newly developed co-culture system, I show that cell-to-cell transmission of α-syn induces intracellular Lewy body-like inclusion body formation and that the FcγRIIB/SHP-1/-2/c-src signaling pathway is involved in it. Therefore, the FcγRIIB-SHP-1/-2/c-src signaling pathway may be a novel therapeutic target for the progression of PD and an in vitro model system provides an efficient tool for further high throughput screening that can be used for developing a therapeutic intervention in PD.

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Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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