Background: Muscular dystrophies are inherited disorders characterized by progressive
skeletal muscle degeneration without curative therapy. The specific defective protein
in each type of muscular dystrophy has been associated with different deleterious factors
that contribute to the progression of the disease. Among these factors, the impairment of
calcium homeostasis, the ubiquitin-proteasome dysfunction, and the oxidative damage of
cellular macromolecules seem to be of central importance. Can these different cellular dysfunctions
be linked by a common pathogenic mechanism susceptible to therapy? A cellular
cysteine network (CYSTEINET) has been proposed previously, as a matrix of interconnected
sensitive cysteine-containing proteins (SCCPs) that in addition to reactive species
and the cysteine/glutathione cycles can regulate metabolic, redox, and survival cellular
pathways by a complex biochemical network of proteins with different functions, but sharing
the same regulatory thiol group.
Objective: Since there are many sensitive cysteine-containing proteins including cysteinedependent
enzymes susceptible to redox modifications at cysteine residues that may contribute
to muscular degeneration, the aim of this review is to propose that cysteinet dysregulation
may explain oxidative damage, calcium disturbances and ubiquitin-proteasome dysfunctions
associated with muscular dystrophies.
Conclusion: The present review proposes that cysteinet dysregulation in muscular dystrophies
may represent a common pathogenic network contributing, in association with the
specific protein dysfunction, to muscular degeneration. In this context, N-acetylcysteine
may have an important role in the restoration of the proposed cysteinet dysregulation associated
with these heterogeneous types of diseases.