Crisis management systems by neurons to defend against systemic immune storms

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15129
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Keio University
• Principal Investigator: MISAWA HIDEMI 慶應義塾大学, 薬学部(芝共立), 教授 (80219617)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ニコチン受容体 / アセチルコリン / コリン作動性抗炎症反応 / 神経毒 / 内在性修飾因子 / 免疫ストーム

Outline of Final Research Achievements

Alpha7-type nicotinic acetylcholine receptor (α7 nAChR) is a therapeutic target for various neurodegenerative and inflammatory conditions. To find a novel α7 nAChR modulator, we picked up Ly6H which is an endogenous protein with structural resemblance to a snake venom α-bungarotoxin. Chimeric receptor channel consisting of the ligand-binding domain of α7 nAChR and the channel domain of the glycine receptor was constructed. Electrophysiological analyses revealed that Ly6H reduced the magnitude of ACh-evoked currents. Next, we established stable cells expressing α7 nAChR, Ric-3 and NACHO, and ACh-induced currents were analyzed. The TARO cells (Triple Alpha7 Ric-3 NACHO cells) showed robust ligand-induced currents. Again, electrophysiological analyses revealed that expression of Ly6H in the TARO cells reduced the magnitude of α7-mediated currents. These results indicate that Ly6H directly binds to the extracellular domain of α7 nAChR and negatively modulates its channel activity.

Free Research Field

神経薬理学