Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy

Stephanie Kourakis; Cara A Timpani; Judy B de Haan; Nuri Gueven; Dirk Fischer; Emma Rybalka

doi:10.1016/j.redox.2020.101803

Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy

Redox Biol. 2021 Jan:38:101803. doi: 10.1016/j.redox.2020.101803. Epub 2020 Nov 18.

Authors

Stephanie Kourakis¹, Cara A Timpani², Judy B de Haan³, Nuri Gueven⁴, Dirk Fischer⁵, Emma Rybalka⁶

Affiliations

¹ College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia. Electronic address: stephanie.kourakis@live.vu.edu.au.
² Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia; Australian Institute for Musculoskeletal Science, Victoria University, St Albans, Victoria, Australia. Electronic address: cara.timpani@vu.edu.au.
³ Oxidative Stress Laboratory, Basic Science Domain, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Australia. Electronic address: judy.dehaan@baker.edu.au.
⁴ School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia. Electronic address: nuri.guven@utas.edu.au.
⁵ Division of Developmental- and Neuropediatrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland. Electronic address: dirk.fischer@ukbb.ch.
⁶ College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia; Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia; Australian Institute for Musculoskeletal Science, Victoria University, St Albans, Victoria, Australia. Electronic address: emma.rybalka@vu.edu.au.

Abstract

Imbalances in redox homeostasis can result in oxidative stress, which is implicated in various pathological conditions including the fatal neuromuscular disease Duchenne Muscular Dystrophy (DMD). DMD is a complicated disease, with many druggable targets at the cellular and molecular level including calcium-mediated muscle degeneration; mitochondrial dysfunction; oxidative stress; inflammation; insufficient muscle regeneration and dysregulated protein and organelle maintenance. Previous investigative therapeutics tended to isolate and focus on just one of these targets and, consequently, therapeutic activity has been limited. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that upregulates many cytoprotective gene products in response to oxidants and other toxic stressors. Unlike other strategies, targeted Nrf2 activation has the potential to simultaneously modulate separate pathological features of DMD to amplify therapeutic benefits. Here, we review the literature providing theoretical context for targeting Nrf2 as a disease modifying treatment against DMD.

Keywords: Duchenne muscular dystrophy; Hormesis; Nrf2; Oxidative stress; Reactive oxygen species; Skeletal muscle.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Disease Models, Animal
Mice
Mice, Inbred mdx
Muscle, Skeletal
Muscular Dystrophy, Duchenne* / drug therapy
Muscular Dystrophy, Duchenne* / genetics
NF-E2-Related Factor 2 / genetics

Substances

NF-E2-Related Factor 2