Development of a new therapeutic strategy targeting increased expression of TDP-43 in amyotrophic lateral sclerosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06583
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Suzuki Hiroaki 東京医科大学, 医学部, 講師 (10424178)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経変性疾患 / 筋萎縮性側索硬化症 / TDP-43

Outline of Final Research Achievements

Amyotrophic lateral sclerosis (ALS) is an incurable motor neurodegenerative disease caused by the death of both upper and lower motor neurons. We have focused on findings that in ALS patients, the expression of Transactive response DNA-binding protein 43 kDa (TDP-43) is up-regulated in the spinal cord containing motor neurons. Previous study has investigated the impact of increased TDP-43 expression on neuronal cells. In this study, we found that TDP-43 causes RNA-binding proteins, which are normally localized in the nucleus, to be mislocalized to the cytoplasm. Furthermore, we elucidated the mechanism underlying mislocalization of RNA-binding proteins.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

ALSを含む運動神経変性疾患の発症機序は十分解明されておらず、また根本的治療法は未だ確立されていない。
ALSの患者数は比較的少数ではあるが、病気のもたらす悲惨さやマイナス面が広く社会的に認知されており、ALSに対する有効な治療法発見のもたらす高齢化社会への影響は大きく、その意義は測りしれないものがある。本研究の成果を基に、将来より有効な薬物が臨床的に実用化され、神経科学領域での学問的な発展に寄与するのみならず、多くのALS患者を救うことで、高齢化社会を迎えた我が国の医療進歩に貢献することと考えられる。