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Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 849426, 19 pages
http://dx.doi.org/10.1155/2010/849426
Review Article

Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies

1Univ Paris-Sud, Centre de Neurosciences Paris-Sud, UMR8195, Orsay, 91405, France
2CNRS, Orsay, 91405, France

Received 16 December 2009; Accepted 14 March 2010

Academic Editor: Meena Upadhyaya

Copyright © 2010 Caroline Perronnet and Cyrille Vaillend. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD), which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression.