Research on dementia therapeutics targeting tau splicing

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kyoto University
• Principal Investigator: Keiko Imamura 京都大学, iPS細胞研究所, 特定拠点講師 (90379652)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: タウ / スプライシング / iPS細胞 / 脳オルガノイド

Outline of Final Research Achievements

The increase in the number of patients with dementia due to the aging of the population has become a growing problem, and there is an urgent need to establish a fundamental treatment for dementia. In Alzheimer's disease and frontotemporal lobar degeneration, which account for the majority of dementia cases, tau protein is an important target for therapeutic intervention because clinical symptoms of dementia are known to emerge with abnormal accumulation of tau protein and neuronal cell death. Tau proteins are classified by splicing mode into 3-repeat tau and 4-repeat tau, with 4-repeat tau promoting β-sheeting and the formation of highly neurotoxic tau oligomers. We have identified candidate drugs for the treatment of dementia that regulate tau expression and splicing in neurons from patients with dementia, and that can reduce tau oligomers and inhibit neuronal cell death.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

認知症の臨床症状は、異常タウタンパク質の蓄積や神経細胞死とともに、出現してくることが知られている。そのため、医療現場における現実的な治療的介入のためには、異常タウタンパク質の蓄積や神経細胞死が治療ターゲットとして重要と考えられる。異常タウタンパク質の蓄積は、認知症を来す多くの神経変性疾患で見られ、これに治療的介入が可能となれば、社会医学的に大きなメリットを有する。