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FcγRIIB mediates the inhibitory effect of aggregated α-synuclein on microglial phagocytosis.

Authors
Choi, YR | Kang, SJ | Kim, JM | Lee, SJ | Jou, I  | Joe, EH  | Park, SM
Citation
Neurobiology of disease, 83. : 90-99, 2015
Journal Title
Neurobiology of disease
ISSN
0969-99611095-953X
Abstract
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Although the etiology of PD has not yet been fully understood, accumulating evidence indicates that neuroinflammation plays a critical role in the progression of PD. 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. In this study, we demonstrated that aggregated α-syn inhibited microglial phagocytosis by activating SHP-1. SHP-1 activation was also observed in A53T α-syn transgenic mice. In addition, aggregated α-syn bound to FcγRIIB on microglia, inducing SHP-1 activation, further inhibiting microglial phagocytosis. Aggregated α-syn upregulated FcγRIIB expression in microglia and upregulated FcγRIIB was also observed in A53T α-syn transgenic mice. These data suggest that aggregated α-syn released from neurons dysregulates microglial immune response through inhibiting microglial phagocytosis, further causing neurodegeneration observed in PD. The interaction of aggregated α-syn and FcγRIIB and further SHP-1 activation can be a new therapeutic target against PD.
MeSH

DOI
10.1016/j.nbd.2015.08.025
PMID
26342897
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
박, 상면  |  조, 은혜  |  주, 일로
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