Common tasks of cytoskeleton and dystrophin in muscular and neurological functions: Perpectives in gene therapy

Duchenne Muscular Dystrophy (DMD) is an inherited disorder characterized by progressive muscular degeneration and cognitive impairment due to mutations in the DMD gene. This disease seriously affects the quality of life of DMD patients causing death due to cardiac and respiratory complications before 30 years of age. Elucidation of the molecular basis for this illness has determined that cytoskeleton and the product of the DMD gene called dystrophin works in a coordinated way to maintain fibre muscle integrity. It is known that cytoskeleton via its association with the integrin complexes modulates migration of stem cells during embryogenesis to give rise to diverse tissues and organs. This association is also important in performing basic neurological processes such as synaptogenesis. Recent findings have shown that the DMD gene is also manifested in the central nervous system where it has different functions from that seen in muscle. Among the most clearly defined tasks of DMD gene in neurons is its involvement in modulating the formation of beta 1-integrin complexes. This chapter describes the scientific path that allowed elucidation of the molecular basis for Duchenne Muscular Dystrophy. The up dated knowledge to explain the role of the DMD gene in neurological functions is also described together with the advances in the design of therapeutic strategies focused on restoration of the DMD gene function in patients.