Dystrophin Induced Cognitive Impairment: Mechanisms, Models and Therapeutic Strategies

Abstract

Existence of conserved domains in dystrophin and its associated complexes provide an opportunity to understand the role of dystrophin associated signalling and its association with neuronal metabolism in a variety of model organisms. We critically reviewed the studies till 2013 through established search engines and databases. Thus, we review the role of dystrophin and its isoforms in different animal models at developmental stages in the neuronal metabolism to enhance the therapeutic strategies. Dystrophin interacts with other proteins in such a way that, when affected, it results in co-morbidities including autism and other neu- ropsychiatric disorders. It is speculated that various signalling molecules may converge to disrupt neuronal metabolism not adequately studied. TGF- β , RhoGAP and CAM mediated signalling molecules are the chief cause of mortalities due to respiratory and cardiac involvement but remain underevaluated targets for cognitive impairment in DMD/BMD. Manipulation of these signalling pathways could be potent intervention in dystrophin induced cognitive impairment while complementary therapeutic approaches may also be helpful in the treatment of cognitive impairment associated with DMD/BMD.