transforming-growth-factor-beta and Neuromuscular-Diseases

Members of the transforming growth factor β (TGF-β) family regulate fundamental physiological process, such as cell growth, differentiation and apoptosis. As a result, defects in this pathway have been linked to uncontrolled proliferation and cancer progression. Here we explore the signal transduction mechanism of TGF-β focusing on therapeutic intervention in human diseases. Like TGF-β, another member of the TGF-β superfamily, activin has been proven to play an important role in maintenance of tissue homeostasis and dysregulation leads to disease. Several studies showed elevated levels of activin are responsible for the development of gonadal tumours and a cachexia-like weight loss syndrome. Discussing the recent advances in approaches developed to antagonise the activin pathway and the encouraging results obtained in animal models, this review presents a therapeutic rationale for targeting the activin pathway in conditions such as cachexia, neuromuscular and/or musculoskeletal disorders.

Topics: Activins; Animals; Antineoplastic Agents; Cachexia; Cell Proliferation; Humans; Musculoskeletal Diseases; Neoplasm Proteins; Neoplasms, Gonadal Tissue; Neuromuscular Diseases; Signal Transduction; Transforming Growth Factor beta

Skeletal muscles become atrophied by muscular disorders such as muscular dystrophy, wasting and even aging. In addition to muscle atrophy, progressive muscle damage, inflammation and replacement of muscle fibers with fibrous and fatty tissues are observed in muscular dystrophy. Neuronal innervation is required for skeletal muscle, and muscles become atrophic when motor neurons are affected by neurodegenerative disorders such as amyotrophic lateral sclerosis. Restoring muscle mass and function lost by diseases such as muscular dystrophy and neurodegenerative disorders is important. There are three rational therapies for muscular dystrophy and related diseases: gene therapy, cell therapy and drug therapy. Gene therapies to replace the defective genes have been tried with various degrees of effectiveness. Multiple myogenic stem cells including satellite cells, bone marrow cells, muscle side population cells, muscle-derived stem cells and mesoangioblast have been characterized. Cell therapies using these stem cells are one of the promising therapies for neuromuscular diseases causing muscle atrophy. As pharmacological drug therapies, increasing skeletal muscle mass by myostatin inhibition is quite promising and will be applied clinically in the near future.

Topics: Amyotrophic Lateral Sclerosis; Animals; Cell Differentiation; Cell Division; Drug Design; Genetic Therapy; Guanine Nucleotide Exchange Factors; Humans; Muscle, Skeletal; Muscular Atrophy; Mutation; Myostatin; Neuromuscular Diseases; Signal Transduction; Stem Cell Transplantation; Superoxide Dismutase; Superoxide Dismutase-1; Transforming Growth Factor beta