Exploration of a new principle for the elimination mechanism of abnormal proteins

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19435
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Tohoku University
• Principal Investigator: Doh-ura Katsumi 東北大学, 医学系研究科, 教授 (00263012)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: プリオン / アルカリフォスファターゼ / 細胞内分解系

Outline of Final Research Achievements

From the preliminary study alkaline phosphatase was thought to provide a clue to the principle of a new intracellular degradation system for persistently accumulating protein aggregates such as prions. The results of our research over the past two years have confirmed that alkaline phosphatase affects prion levels in persistently prion-infected cells, but have not provided any clues to elucidate the mechanism of this effect. In addition, it was hypothesized that the alkaline environment at the subcellular domain where alkaline phosphatase acts may be involved in prion degradation and elimination, but it is still undetermined whether this hypothesis is correct or not, and further studies are needed.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

難分解性蛋白質凝集体が細胞内でどのように分解・代謝されているのか、その基本原理は不明であり、既知の分解系だけでは説明できない。新たな基本原理の究明は、難分解性蛋白質凝集体が細胞や組織中に蓄積する様々な疾患に対して、新たな治療開発の糸口を与えてくれる可能性がある。難分解性蛋白質凝集体の代表であるプリオンにおいて、アルカリフォスファターゼとの関係に光をあてた本研究は、この新たな基本原理の究明に結びつく可能性を残し、アルカリフォスファターゼの新たな機能解明につながることが期待される。