Mechanisms of expression and action of neurodegeneration-promoting glycan bisecting GlcNAc

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07356
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Gifu University
• Principal Investigator: Kizuka Yasuhiko 岐阜大学, 研究推進・社会連携機構, 准教授 (20564743)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 糖鎖生物学 / 糖鎖 / bisecting GlcNAc / バイセクト糖鎖 / 脳 / HNK-1 / GnT-V / PRMT1

Outline of Final Research Achievements

The aim of this study is to elucidate the mechanisms of expression and functions of neural glycans. In particular, we focus on bisected glycans which have been found to promote Alzheimer's disease. Major achievements of this project are as follows. 1) We for the first time solved the 3D structure of N-glycan branching enzyme, GnT-V, that is highly related to the expression of bisected glycans (Nagae et al., Nat. Common., 2018). 2) We revealed that several terminal structures of in N-glycans are commonly increased in the brain of the mutant mice lacking bisected glycans, demonstrating a novel function of bisected glycans as a suppressor of N-glycan maturation.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、バイセクト糖鎖のN型糖鎖抑制因子としての生理機能が明らかになったとともに、バイセクト糖鎖の発現にも関わるGnT-Vの立体構造を世界に先駆けて解明した。バイセクト糖鎖はアルツハイマー病の発症や進行と深く関わり、アルツハイマー病患者でその発現量が増加していることから、患者脳で本糖鎖が発現することの意義の解明に近づいたと言える。またGnT-Vはがんの悪性化を引き起こす糖鎖分岐構造を形成することから、その立体構造の解明によってがんの悪性化を抑える化合物のデザインが可能になった。