筋ジストロフィーの進行を遅らせる発見(Discovery Slows Down Muscular Dystrophy)

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2023-05-24 ヒューストン大学(UH)

◆テキサス大学ヒューストン校の研究チームは、免疫系のタンパク質であるTAK1を操作することで、デュシェンヌ型筋ジストロフィー(DMD)の進行を遅らせ、筋肉の機能を改善できる可能性があることを報告しています。
◆DMDは遺伝性の神経筋疾患で、患者は筋肉の消耗や歩行困難などを経験します。研究ではTAK1を標的にすることで、筋繊維の死を抑制し、病気の進行を遅らせる効果が示されました。これにより、DMDの治療に新たなアプローチが期待されています。

<関連情報>

TAK1の標的制御がDMDマウスモデルにおけるジストロフィノパシーに対抗する Targeted regulation of TAK1 counteracts dystrophinopathy in a DMD mouse model

Anirban Roy, Tatiana E. Koike, Aniket S. Joshi, Meiricris Tomaz da Silva, Kavya Mathukumalli, Mingfu Wu, and Ashok Kumar
JCI Insight  Published April 18, 2023
DOI:https://doi.org/10.1172/jci.insight.164768

筋ジストロフィーの進行を遅らせる発見(Discovery Slows Down Muscular Dystrophy)

Abstract

Muscular dystrophies make up a group of genetic neuromuscular disorders that involve severe muscle wasting. TGF-β–activated kinase 1 (TAK1) is an important signaling protein that regulates cell survival, growth, and inflammation. TAK1 has been recently found to promote myofiber growth in the skeletal muscle of adult mice. However, the role of TAK1 in muscle diseases remains poorly understood. In the present study, we have investigated how TAK1 affects the progression of dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD). TAK1 is highly activated in the dystrophic muscle of mdx mice during the peak necrotic phase. While targeted inducible inactivation of TAK1 inhibits myofiber injury in young mdx mice, it results in reduced muscle mass and contractile function. TAK1 inactivation also causes loss of muscle mass in adult mdx mice. By contrast, forced activation of TAK1 through overexpression of TAK1 and TAB1 induces myofiber growth without having any deleterious effect on muscle histopathology. Collectively, our results suggest that TAK1 is a positive regulator of skeletal muscle mass and that targeted regulation of TAK1 can suppress myonecrosis and ameliorate disease progression in DMD.

医療・健康
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