Investigating mechanisms of tau-induced neurotxicity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: Sahara Naruhiko 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 上席研究員 (40261185)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: タウ / モデル動物 / 毒性伝播

Outline of Final Research Achievements

Neuropathological observations revealed the existence of abundant inclusions with the properties of amyloid fibrils. Most neurodegenerative diseases are defined by multiple types of inclusion consisting of aggregated forms of protein or peptide called proteinopathy. The microtubule-associated protein tau abnormally aggregates into intracellular, filamentous inclusions (NFTs) in brains of individuals with neurodegenerative diseases including Alzheimer’s disease (AD). NFTs are closely associated with the severity of brain function loss in AD. Thus, making tau protein a target in the treatment of AD has become a major therapeutic strategy. Here, we established cellular and mouse models of tauopathy showing cell-cell propagation and pathological tau accumulation. In addition, tauopathy-linked microglial phenotypic change distinct was observed in the mouse model of tauopathy. These models will be essential tools for investigating mechanisms of tau-induced neurotoxicity.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病を代表とする多くの認知症では、タウ蛋白質の細胞内沈着を病理学的特徴としたタウオパチーと呼ばれる疾患群が存在し、タウ病態は神経細胞死と密接に関係している。タウ病態の進行を食い止める方法を確立することが、多くの認知症の治療に結びつくと考えられることから、本研究で掲げたタウ毒性制御メカニズムの解明は直近の課題であると言える。