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

Abstract

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.

• Authors: Yu Ree Choi, Seon-Heui Cha, Seo-Jun Kang, Jae-Bong Kim, Ilo Jou, Sang Myun Park
• Journal: Cell reports (Cell Rep) Vol. 22 Issue 1 Pg. 136-148 (01 02 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 29298416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• FCGR2B protein, human
• Prions
• Receptors, IgG
• SNCA protein, human
• alpha-Synuclein
• PTPN11 protein, human
• PTPN6 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Protein Tyrosine Phosphatase, Non-Receptor Type 6

Topics

• Cell Line
• Humans
• Neurons (metabolism, pathology)
• Parkinson Disease (genetics, metabolism, pathology)
• Prions
• Protein Transport (genetics)
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics, metabolism)
• Protein Tyrosine Phosphatase, Non-Receptor Type 6 (genetics, metabolism)
• Receptors, IgG (genetics, metabolism)
• Signal Transduction
• alpha-Synuclein (genetics, metabolism)