Targeting Nrf2 for the treatment of Duchenne Muscular Dystrophy
Stephanie Kourakis,
Cara A. Timpani,
Judy B. de Haan,
Nuri Gueven,
Dirk Fischer,
Emma Rybalka
Affiliations
Stephanie Kourakis
College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia
Cara A. Timpani
Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia; Australian Institute for Musculoskeletal Science, Victoria University, St Albans, Victoria, Australia
Judy B. de Haan
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
Nuri Gueven
School of Pharmacy and Pharmacology, University of Tasmania, Hobart, Tasmania, Australia
Dirk Fischer
Division of Developmental- and Neuropediatrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
Emma Rybalka
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; Corresponding author. Institute for Health and Sport, Victoria University, PO Box 14428, Melbourne City MC, Victoria, 8001, Australia.
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.
