Language
Country/Area
No result found
Why does dystrophin deficiency cause progressive muscle atrophy? Reveal the science behind it!
Dystrophin is a stick-shaped cytoplasmic protein that is essential for connecting the muscle fiber's cytoskeleton to its surrounding extracellular matrix. This complex is called costamere or dystrophin-associated protein complex (DAPC), and is co-localized with dystrophin in costamere in different muscle proteins, such as α-dystrobrevin, syncoilin, synemin, etc.
Whenever dystrophin is missing or abnormally expressed, it will affect the structure and function of muscle fibers, causing various types of muscular dystrophy, especially Duchenne muscular dystrophy (DMD). The root cause of these conditions often stems from mutations in the DMD gene, which is the largest known gene in the human body, covering 2.4 megabase pairs and located on the X chromosome.
Function of Dystrophin
Dystrophin's main function is to connect the surface of muscle cells to their internal structures. It connects actin to supporting proteins on the membrane, which in turn connect to the outermost layer of muscle fibers and ultimately to the inner fibrous membrane of the muscle. When dystrophin is missing, muscle fiber stability becomes fragile, which results in decreased muscle strength and a progressive loss of muscle strength.
Muscles lacking dystrophin cannot resist the tearing force during exercise and are prone to injury. Over time, the muscles will gradually atrophy.
Pathology of muscle atrophy
Dystrophin deficiency has been identified as an underlying cause of muscular dystrophy. Genetic defects in Duchenne and Becker muscular dystrophies result from exon deletions in the dystrophin gene. In normal skeletal muscle tissue, the content of dystrophin is very small, but its absence or abnormal expression can lead to severe muscle damage.
As the disease progresses, most DMD patients become wheelchair dependent in the early stages, and the hypertrophy of the heart eventually leads to death in their twenties and thirties.
Research Progress
Currently, various models have been used to study the genetic defects of DMD, such as mdx mice and GRMD dogs. mdx mice possess a mutation that causes dystrophin shortening, a model useful for observing the pathology of muscle degeneration. Dogs with GRMD can develop clinically relevant lesions as early as eight weeks of age, which gradually worsen over time.
Exploration of treatment methods
One treatment, Delandistrogene moxeparvovec, uses systemic gene transfer to provide the muscles with the microscopic dystrophin they need to improve muscle function in patients. While this treatment has shown promise in research, further research is needed to determine its long-term effects.
Recent studies have pointed out that dystrophin and its related complexes play an important role in cell signaling and regulation, which has increased interest in therapeutic potential.
Reflection and Outlook
With the advancement of science and technology, our understanding of dystrophin is getting deeper and deeper. However, there are still many unknowns that need to be explored as to how to effectively address the health challenges posed by their absence. Can the scientific community find an effective treatment for these muscular dystrophies and save the lives of those affected?
