Understanding for Alzheimer's disease pathogenesis and the development of novel target for therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: SUZUKI Toshiharu 北海道大学, 薬学研究科(研究院), 教授 (80179233)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: アルツハイマー病 / 老化 / 認知症 / APP

Outline of Final Research Achievements

Pathogenesis of sporadic Alzheimer's disease (AD) is various. To reveal these, this research focused on (1) the function of X11 and/or X11L, and (2) mechanism to cleave substrate proteins by gamma-secretase. X11 binds to a target protein in non-phosphorylated state, while X11L associate same target in phosphorylation-mimicked state. We identified Src protein kinase as a potential kinase to phosphorylate X11L. In X11 and X11L genes double-KO mice, a micro-localization of some of neurotransmitter receptors was disturbed, which may be a cause of amyloid-beta dependent aberrant signal transduction inducing neuronal cell death. Furthermore, this research found that changes of lipid composition within cell membrane can induce altered gamma-cleavages of substrates such as APP and Alcadein. Taken together , these findings suggest a novel pathogenic way of AD and target of drug development.

Free Research Field

生化学