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

Authors
Choi, YR; Cha, SH; Kang, SJ; Kim, JB; Jou, I; Park, SM
Citation
Cell reports, 22(1):136-148, 2018
Journal Title
Cell reports
ISSN
2211-1247
Abstract
Recent evidence of prion-like propagation of alpha-synuclein (alpha-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 FcgammaRIIB expressed in neurons functions as a receptor for alpha-syn fibrils and mediates cell-to-cell transmission of alpha-syn. SHP-1 and 2 are activated downstream by alpha-syn fibrils through FcgammaRIIB and play an important role in cell-to-cell transmission of alpha-syn. Also, taking advantage of a co-culture system, we show that cell-to-cell transmission of alpha-syn induces intracellular Lewy body-like inclusion body formation and that the FcgammaRIIB/SHP-1/2 signaling pathway is involved in it. Therefore, the FcgammaRIIB-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.
MeSH terms
Cell LineHumansNeurons/metabolism*Neurons/pathologyParkinson Disease/geneticsParkinson Disease/metabolism*Parkinson Disease/pathologyPrions*Protein Transport/geneticsProtein Tyrosine Phosphatase, Non-Receptor Type 11/geneticsProtein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism*Protein Tyrosine Phosphatase, Non-Receptor Type 6/geneticsProtein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism*Receptors, IgG/geneticsReceptors, IgG/metabolism*Signal Transduction*alpha-Synuclein/geneticsalpha-Synuclein/metabolism*
DOI
10.1016/j.celrep.2017.12.009
PMID
29298416
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로박, 상면
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