Mitochondrial regulation by MITOL and diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Gakushuin University
• Principal Investigator: INATOME RYOKO 学習院大学, 理学部, EF共同研究員 (90408691)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ミトコンドリア / アルツハイマー病

Outline of Final Research Achievements

We have previously elucidated the mechanism by which the loss of function of the mitochondrial ubiquitin ligase MITOL significantly exacerbates the pathophysiology of Alzheimer's disease. Based on these research results, we hypothesized that a drug that increases the activity of MITOL would be a potential therapeutic agent for Alzheimer's disease, and as a result of our search for a drug that activates MITOL, we succeeded in identifying a drug named MitoRubin. When MitoRubin was administered to Alzheimer's disease model cells expressing aggregated tau, they found that the aggregation of abnormal tau was markedly inhibited. This degradation of aggregated tau was caused by MITOL through ubiquitin-proteasome pathway. These results strongly suggest that MitoRubin is a potential therapeutic agent for Alzheimer's disease.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は国内外で精力的に研究がされているが、ミトコンドリア機能との関連に着目した研究報告は未だ数が少なく、その実態が明らかにされていない。私たちの研究はミトコンドリアの機能低下がアルツハイマー病の原因と考えられているAβプラークの毒性亢進とタウ凝集形成の分子メカニズムに密接に関連することを示唆したものであり、ミトコンドリアを標的にした新たな治療法の開発に道を拓くものである。実際にマイトルビンはミトコンドリアを活性化する薬剤であり、アルツハイマー病の治療薬候補として有望である。