Elucidation of molecular mechanism of neural differentiation mediated by purinosome formation by the Nwd1

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20701
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Waseda University
• Principal Investigator: Yamada Seiya 早稲田大学, 人間科学学術院, 助教 (70907146)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 神経幹細胞 / Nwd1 / プリノソーム / プリン代謝

Outline of Final Research Achievements

In normal brain development, the control of two pathways producing purine metabolite is essential, and abnormalities in this process are implicated in various psychiatric disorders, although the details of their spatiotemporal regulation are unclear. In addition, it has been demonstrated that the enzymatic reactions for de novo purine synthesis is occurred within a large protein complex called purinosome. We identified Nwd1 gene, which is abundantly expressed in neural stem cells, is involved in purinosome formation and controls proliferation and differentiation of neural stem cells. This study revealed a spatiotemporal functional and localization of purine metabolism enzymes during neurogenesis, as well as a Nwd1 physiological function using Nwd1 knockout mice.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

プリン合成経路の時空間的制御の解明は、進化の過程で巨大な大脳を獲得した哺乳類に特有の高次脳機能を司る分子メカニズムの一端および、その破綻から起きる精神疾患や神経発達障害の追究に寄与できると期待される。さらに、プリン代謝の異常による疾患は種々のがんとの関連も多数報告されている。細胞外環境に依存するプリン合成経路の切り替えは、神経幹細胞だけでなく、がん幹細胞や他の組織幹細胞にも共通して存在する可能性がある。今後、抗がん剤をはじめとする創薬開発にとって貴重な視点を提供することが期待される。