NRF2 signaling cascade in amyotrophic lateral sclerosis:bridging the gap between promise and reality  

作　　者：Pauline Tarot Christelle Lasbleiz Jean-Charles Liévens 

机构地区：[1]MMDN,Univ Montpellier,EPHE,INSERM,Montpellier,France [2]CNRS,Paris,France,EPHE,INSERM,Montpellier,France

出　　处：《Neural Regeneration Research》2024年第5期1006-1012,共7页中国神经再生研究（英文版）

基　　金：supported by a grant from the Association Française contre les Myopathies(AFM Téléthon;grant 23667,to JCL).

摘　　要：Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor neurons.Symptoms include muscle weakness and atrophy,spasticity,and progressive paralysis.Currently,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral sclerosis.The only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial effects.The difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis pathogenesis.Among mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious circle.Sharpening the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and inflammation.We here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.

关 键 词：amyotrophic lateral sclerosis C9orf72 NRF2 oxidative defense oxidative stress SULFORAPHANE superoxide dismutase 1 TDP43 

分 类 号：R744.8[医药卫生—神经病学与精神病学]