ALTERED GENE EXPRESSION PATHWAYS IN DUCHENNE MUSCULAR DYSTROPHY

Abstract

Duchenne muscular dystrophy (DMD) is caused by the absence of functional dystrophin (Blake et al. 2002). Dystrophin is a cytoskeleton protein normally expressed in the inner face of the plasma membrane (Ahn and Kunkel 1993). In normal skeletal muscle, dystrophin is associated with a complex of glycoproteins known as dystrophin-associated proteins (DAPs), providing a linkage between the extracellular matrix (ECM) and cytoskeleton (Batchelor and Winder 2006). Lack of dystrophin in dystrophic muscle results in loss of the complex integrity and allegedly impairs the stability of the plasma membrane causing mechanical stress fragility, and an increase in Ca2+ permeability (Alderton and Steinhardt 2000). But the pathophysiology of muscular dystrophy is not only explained by this increased mechanical fragility and a role for dystrophin and DAPs has been suggested as being part of a protein signaling complex involved in cell survival (Rando 2001). In this chapter we discuss evidence of such a role, which may evidence possible interactions between dystrophin and proteins other than those involved in DAP and possible cell location of dystrophin in regions other than the sarcolemma cytoskeleton.