Targeting PKCθ in skeletal muscle and muscle diseases: good or bad?

Protein kinase C-theta (PKCθ) is a member of the novel calcium-indipendent protein kinase C (PKC) family, with a relatively selective tissue distribution. Most studies have focussed on its unique role in T lymphocyte activation and suggest that inhibition of PKC could represent a novel therapeutic approach in the treatment of chronic inflammation, autoimmunity and allograft rejection. However, considering that PKC is also expressed in other cell types, including skeletal muscle cells, it is important to understand its function in different tissues before proposing it as a molecular target for the treatment of immune mediated diseases. A number of studies have highlighted the role of PKC in mediating several intracellular pathways regulating muscle cell development, homeostasis and remodelling, although a comprehensive picture is still lacking. Moreover, we recently showed that lack of PKC in a mouse model of Duchenne Muscular Dystrophy ameliorates the progression of the disease. Here, we review new developments in our understanding of the involvement of PKC in intracellular mechanisms regulating skeletal muscle development, growth and maintenance under physiological conditions, and recent advances showing a hitherto unrecognized role of PKC in promoting muscular dystrophy.