Browsing Master's Theses by Authors
Molecular Mechanisms that Underlie Duchenne Muscular DystrophyNelson, Mark; Lybarger, Lonnie; Babaria, Arati; Elliott, David; Pannabecker, Thomas; Lybarger, Lonnie; Nelson, Mark (The University of Arizona., 2016)Duchenne muscular dystrophy is an inherited, X-linked recessive skeletal muscle disorder that is characterized by mutations in the dystrophin gene . Therefore, the disease affects primarily males and women are typically carriers. 1 in 3500 males in the United States are affected . Dystrophin is a critical, large scaffolding protein in the dystrophin-glycoprotein complex found at the sarcolemma of skeletal muscle . The complex helps maintain sarcolemma integrity and stability during muscle contractions by coupling the extracellular matrix proteins to the intracellular cytoskeleton in skeletal muscle . Loss-of-function mutations in the dystrophin protein affect all skeletal muscle found throughout the human body. The 427 kD protein is also present in cardiac muscle, the brain, and peripheral nerves, thus affecting these tissues over time, as well . One theory suggests the weakened stability of the dystrophin-glycoprotein complex when dystrophin is not expressed results in transient membrane tears during contraction, which permit pathological calcium influx . Damaged skeletal muscle results in repair and regeneration of the tissue however, continual damage over time (referred to as muscle wasting) results in extensive fibrosis and loss of muscle fibers. The purpose of this thesis is to provide a comprehensive review on several molecular mechanisms that underlie Duchenne muscular dystrophy and to investigate current treatments and propose potential therapeutic targets for future research.