Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy.
Silvia Rosanna CasatiDavide CerviaPaulina Roux-BiejatClaudia MoscheniCristiana PerrottaClara De PalmaPublished in: Cells (2024)
Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence of functional dystrophin in DMD patients reduces sarcolemma stiffness and increases contraction damage, triggering a cascade of events leading to muscle cell degeneration, chronic inflammation, and deposition of fibrotic and adipose tissue. Efforts in the last decade have led to the clinical approval of novel drugs for DMD that aim to restore dystrophin function. However, combination therapies able to restore dystrophin expression and target the myriad of cellular events found impaired in dystrophic muscle are desirable. Muscles are higher energy consumers susceptible to mitochondrial defects. Mitochondria generate a significant source of reactive oxygen species (ROS), and they are, in turn, sensitive to proper redox balance. In both DMD patients and animal models there is compelling evidence that mitochondrial impairments have a key role in the failure of energy homeostasis. Here, we highlighted the main aspects of mitochondrial dysfunction and oxidative stress in DMD and discussed the recent findings linked to mitochondria/ROS-targeted molecules as a therapeutic approach. In this respect, dual targeting of both mitochondria and redox homeostasis emerges as a potential clinical option in DMD.
Keyphrases
- duchenne muscular dystrophy
- reactive oxygen species
- oxidative stress
- cell death
- muscular dystrophy
- end stage renal disease
- adipose tissue
- newly diagnosed
- skeletal muscle
- ejection fraction
- chronic kidney disease
- prognostic factors
- cancer therapy
- multiple sclerosis
- type diabetes
- peritoneal dialysis
- gene expression
- single cell
- insulin resistance
- signaling pathway
- systemic sclerosis
- drug delivery
- dna methylation
- climate change
- mesenchymal stem cells
- diabetic rats
- idiopathic pulmonary fibrosis
- copy number
- drug induced
- heat shock
- smooth muscle
- heat shock protein