Cooperative function of alpha-synuclein and tau during brain development

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06821
• 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: Osaka Metropolitan University (2022-2023); Osaka City University (2021)
• Principal Investigator: Jin Mingyue 大阪公立大学, 大学院医学研究科, 研究員 (60740404)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脳の発生

Outline of Final Research Achievements

Abnormal intracellular aggregation of αSyn and/or tau in the human brains define multiple forms of neurodegenerative diseases including AD and PD. In addition, coexistence of αSyn and tau aggregates in tauopathies and synucleinopathies indicates a strong cross-talk between two proteins during pathogenesis. Despite their disease relevance, the normal physiological functions and roles of these two proteins have remained elusive, as mice with knockout of either of these proteins do not present overt phenotypes. To address this issue, we simultaneously removed Snca and Mapt genes and generated αSyn-/-tau-/- mice. Through this research project we revealed that αSyn and tau participate in proper neurogenesis and gliogenesis via controlling of Notch signaling and microtubule reorganization. Functional cross-talk between αSyn and tau during corticogenesis will provide new mechanistic insights for the pathogenesis of neurodegenerative diseases caused by aberrant αSyn and/or tau.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

αSynとtauが脳への異常蓄積は神経変性疾患の発症原因となるが、その生理的な機能は十分解明されていない。臨床では、PDは主に運動障害を示すのに対し、AD患者は主に認知機能の低下を示している。しかし、神経変性疾患患者の死後解剖では、αSynとtauが一緒に病変部に異常蓄積することが多数報告され、αSynとtau両者が認知機能と運動の制御に密接に関わっていることを示唆した。本研究は、これまで独立して研究されていたαSynとtauが機能的クロストークを持つことを初めて明らかにし、異なる神経変性疾患にまたがる共通病態、特にPDとAD間に存在する共通関連性を特定するのに重要な証拠を提示することになる。