Prion-like Propagation of α-Synuclein Is Regulated by the FcγRIIB-SHP-1/2 Signaling Pathway in Neurons

Publication date: 2 January 2018
Source:Cell Reports, Volume 22, Issue 1
Author(s): Yu Ree Choi, Seon-Heui Cha, Seo-Jun Kang, Jae-Bong Kim, Ilo Jou, Sang Myun Park
Recent evidence of prion-like propagation of α-synuclein (α-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson's disease (PD) and to develop therapeutic strategies. Here, we 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 and 2 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 co-culture system, we show that cell-to-cell transmission of α-syn induces intracellular Lewy body-like inclusion body formation and that the FcγRIIB/SHP-1/2 signaling pathway is involved in it. Therefore, the FcγRIIB-SHP-1/-2 signaling pathway may be a therapeutic target for the progression of PD. The in vitro system is an efficient tool for further high-throughput screening that can be used for developing a therapeutic intervention in PD.

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Teaser

Prion-like propagation of α-synuclein (α-syn) may contribute to the progression of Parkinson's disease. Choi et al. demonstrate that FcγRIIB functions as a receptor for α-syn fibrils and that the FcγRIIB-SHP-1/2 signaling pathway mediates cell-to-cell transmission of α-syn. Blocking this signaling pathway attenuates transmission, suppressing Lewy body-like inclusion body formation.


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