Elucidation of the Antioxidant Mechanism of Thioredoxin in Amyotrophic Lateral Sclerosis and Its Application in Developing Novel Therapeutic Agents

2024 Fiscal Year Final Research Report

• Project/Area Number: 20K16172
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tottori University
• Principal Investigator: Kitao Shinichiro 鳥取大学, 医学部附属病院, 助教 (60724804)
• Project Period (FY): 2020-04-01 – 2025-03-31
• Keywords: 筋萎縮性側索硬化症 / チオレドキシン

Outline of Final Research Achievements

Thioredoxin (TRX) is a multifunctional protein that facilitates the elimination of reactive oxygen species (ROS), which are detrimental to cellular homeostasis. Overexpression of TRX may inhibit neuronal cell death in the spinal cord and ameliorate severe motor impairment in amyotrophic lateral sclerosis (ALS). In this study, we generated TRX-overexpressing ALS model mice (TRX-ALS) and evaluated their motor performance. Furthermore, spinal cord neurons were analyzed both morphologically and functionally. TRX-ALS mice exhibited significantly improved motor function compared to conventional ALS model mice, along with a significant enhancement of mitochondrial function within spinal cord neurons.

Free Research Field

人体病理学関連 / 放射線科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、チオレドキシン（TRX）の過剰発現がALSモデルにおいて脊髄神経細胞のミトコンドリア機能を改善し、運動機能を有意に改善することが示された。これは、TRXの抗酸化作用がALSの病態進行を抑制しうることを示唆しており、ALSに対する新規治療戦略の分子基盤として重要な学術的意義を持つとともに、将来的な治療薬開発への応用が期待される。