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

Neurobiology of Disease
Yu Ree ChoiSang Myun Park

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 phagocyt...Continue Reading

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Citations

Mar 15, 2016·Frontiers in Aging Neuroscience·Chaosi LiLifeng Yang
Nov 27, 2018·The European Journal of Neuroscience·Malú G Tansey, Marina Romero-Ramos
Jan 15, 2019·Cellular and Molecular Neurobiology·Alice FilippiniIsabella Russo
May 6, 2019·Brain : a Journal of Neurology·C Warren OlanowJeffrey H Kordower
May 7, 2020·EMBO Reports·Yu Ree ChoiSang Myun Park
Aug 22, 2018·Frontiers in Cellular Neuroscience·Sara A Ferreira, Marina Romero-Ramos
May 8, 2018·Experimental Neurobiology·Eun-Hye JoeSangmyun Park
Nov 16, 2018·Experimental Neurobiology·Seo-Jun KangSang Myun Park
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Mar 27, 2020·Frontiers in Cellular Neuroscience·Deqiang HanZhiguo Chen
Aug 11, 2020·Current Tropical Medicine Reports·Amy Y VittorSteven T DeKosky
Dec 18, 2020·The FEBS Journal·Yu Ree ChoiSang Myun Park
Feb 9, 2021·Acta Neuropathologica·Ashley S HarmsMarina Romero-Ramos
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