Elucidation of a neurodegenerative mechanism induced by a new Alzheimer's disease drug target and its inhibition

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293075
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Foundation for Biomedical Research and Innovation
• Principal Investigator: Hoshi Minako 公益財団法人先端医療振興財団, その他部局等, 研究員 (30374010)
• Co-Investigator(Kenkyū-buntansha): 廣明 秀一 名古屋大学, その他の研究科, 教授 (10336589) ; 大西 隆之 公益財団法人先端医療振興財団, その他部局等, 研究員 (30418959)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経細胞死 / 神経変性疾患 / ナトリウムポンプ / 立体構造

Outline of Final Research Achievements

Alzheimer's disease is a disorder that causes cognitive decline due to death of mature neurons, but the cause and mechanism of this death of mature neurons had been unknown.
In this work, we showed for the first time that an assembly, a 30-mer of amyloid-β protein, (which we termed amylospheroids) binds to the sodium pump essential for the survival and function of mature neurons and cause death of mature neurons by suppressing the pump function through this binding. In addition, we showed that peptides that bind to amylospheroids inhibit the death of mature neurons by blocking amylospheroids' binding to the sodium pump, and opened up a path to treatment.
We also clarified the tertiary structure of amylospheroids and showed that amylospheroids havd a specific three-dimensional structure.

Free Research Field

病態医化学