Muscular Dystrophy

What is Muscular Dystrophy (MD)?

Muscular dystrophy (MD) is a group of genetic disorders characterized by progressive weakness and degeneration of skeletal muscles, which are the muscles that control movement. There are many different types of muscular dystrophy, each caused by mutations in specific genes responsible for the structure and function of muscle cells.

The most common and well-known type of muscular dystrophy is Duchenne muscular dystrophy (DMD), which primarily affects boys and typically becomes apparent in early childhood. Other types include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, and limb-girdle muscular dystrophy, among others.

What is the relationship between MD and oxidative stress?

The relationship between muscular dystrophy (MD) and oxidative stress is complex and multifaceted. While oxidative stress is not considered the primary cause of muscular dystrophy, it plays a significant role in the pathogenesis and progression of the disease. Here’s how MD and oxidative stress are interconnected:

• Inflammation and Immune Response: In many forms of muscular dystrophy, including Duchenne muscular dystrophy (DMD), the primary cause of muscle degeneration is genetic mutations that result in the absence or dysfunction of specific proteins essential for muscle structure and function. This genetic defect triggers an inflammatory response and immune cell infiltration into the muscle tissue. Immune cells release pro-inflammatory cytokines and reactive oxygen species (ROS), leading to oxidative stress and further damage to muscle fibers.

• Muscle Degeneration and Regeneration: In MD, the absence or dysfunction of key proteins compromises the integrity and stability of muscle fibers, making them more susceptible to damage and degeneration. Muscle degeneration results in the release of cellular contents, including myoglobin, creatine kinase, and other molecules, which can induce oxidative stress and inflammation in neighboring cells. Additionally, impaired muscle regeneration and repair mechanisms in MD contribute to the accumulation of oxidative damage over time.

• Mitochondrial Dysfunction: Mitochondria are the primary producers of cellular energy (ATP) and play a crucial role in muscle function. In MD, mitochondrial dysfunction is commonly observed, leading to impaired energy production, increased production of ROS, and oxidative stress. Mitochondrial abnormalities may arise from genetic defects, inflammatory cytokines, or oxidative damage to mitochondrial DNA, proteins, and lipids.

• Antioxidant Defenses: To counteract the harmful effects of oxidative stress, cells have antioxidant defense mechanisms that scavenge ROS and protect against oxidative damage. However, in MD, the balance between ROS production and antioxidant defenses is disrupted, leading to oxidative stress overload. Reduced levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, have been observed in muscles of individuals with MD, further exacerbating oxidative damage.

• Secondary Pathways of Damage: Oxidative stress not only directly damages muscle fibers but also activates secondary pathways of damage, including lipid peroxidation, protein oxidation, and DNA damage. These secondary products of oxidative stress can further impair cellular function, exacerbate inflammation, and contribute to disease progression in MD.

Overall, oxidative stress is intimately involved in the pathogenesis and progression of muscular dystrophy, contributing to muscle degeneration, inflammation, impaired regeneration, and functional decline.