Comprehensive Functional Analysis of Genome Resources Aimed at Elucidating the Pathomechanisms of Tauopathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02837
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Niigata University
• Principal Investigator: Sugie Atsushi 新潟大学, 脳研究所, 准教授 (50777000)
• Co-Investigator(Kenkyū-buntansha): 池内 健 新潟大学, 脳研究所, 教授 (20372469) ; 新田 陽平 新潟大学, 脳研究所, 特任助教 (30800429)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経変性疾患 / タウオパチー / ショウジョウバエ

Outline of Final Research Achievements

Tauopathy, a group of diseases including Alzheimer's disease, is characterized by the accumulation of tau protein within cells. We analyzed the largest domestic tauopathy genome resource, identifying potential causative genes that harbor low-frequency missense mutations. Utilizing fruit flies, we established an experimental model to monitor neurodegenerative changes and synaptic loss in optic nerve axons. Additionally, we developed MeDUsA, an automated system for quantifying neurodegeneration. Through this, we assessed the impact of mutations and explored the functionality of genes associated with tauopathy risk; however, no significant differences were detected. Our research also led to the discovery of mutations responsible for rare diseases and the development of corresponding pathological models. These findings significantly enhance our understanding of neurodegenerative diseases.

Free Research Field

神経科学、遺伝学

Academic Significance and Societal Importance of the Research Achievements

私たちが特定した低頻度のミスセンス変異含む遺伝子は、タウオパチーの病態メカニズムを理解する鍵となり得ます。ショウジョウバエを用いた視神経軸索の変性とシナプス喪失のモニタリング実験モデルは、疾患発症の遺伝的背景を探る新たなアプローチを提供し、MeDUsAを用いた自動定量化技術は研究の効率を大幅に向上させています。さらに、希少疾患の原因遺伝子の特定や新しい病態モデルの開発は、より広範な神経変性疾患の治療法開発に寄与する可能性があります。これらの研究成果は、学術的にも社会的にも重要であり、神経変性疾患の診断、治療、予防の進展に貢献することが期待されます。