Elucidation of the mechanism of cerebral amyloid angiopathy by moonlighting glycolytic enzyme

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16919
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kumamoto University
• Principal Investigator: Inoue Yasuteru 熊本大学, 大学院生命科学研究部(医), 特任助教 (00806408)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: アミロイドβ / 脳出血 / 認知症 / アルツハイマー病

Outline of Final Research Achievements

In the present study, we focused on α-enolase (ENO1), well known glycolytic enzyme crucial for glucose metabolism, which is identified as up-regulated protein in brain samples from AD and CAA by proteomic analyses. Although ENO1 has been shown to possess multifunctional roles as a heat-shock protein and binding protein of cytoskeleton or chromatin structure, exact function of ENO1 in AD and CAA pathogenesis are not determined. We identified the novel function of ENO1 to directly interact with Aβ and inhibit its fibril formation, disrupt Aβ fibrils, and further to attenuate its cytotoxicities. In addition, we found that enzymatically inactivated ENO1 failed to inhibit Aβ fibril formation and disruption of Aβ fibrils. The proteolytic activity of ENO1 may underlie cytoprotective effect and clearance of Aβ from brain in AD and CAA and may be　valuable therapeutic target.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

α-エノラーゼを治療ターゲットとした核酸医薬を開発することで、Aβタンパク質の蓄積の制御につながる治療法を創出できる可能性がある。その他、早期診断のためのバイオマーカーなど新たな医療シーズへの発展・展開が見込まれる意義ある研究成果と考える。