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Brain Sci. 2015, 5(3), 275-298; doi:10.3390/brainsci5030275

Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

1
Department of Medical Genetics, University of Alberta Faculty of Medicine and Dentistry
2
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan
3
Muscular Dystrophy Canada Research Chair, 8812-112 St, Edmonton, AB T6G 2H7, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Stephen D. Meriney
Received: 12 May 2015 / Revised: 29 June 2015 / Accepted: 21 July 2015 / Published: 29 July 2015
(This article belongs to the Special Issue Exercise and Brain Function)
View Full-Text   |   Download PDF [604 KB, uploaded 29 July 2015]   |  

Abstract

Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain. View Full-Text
Keywords: dystrophin; dystrophin-glycoprotein complex (DGC); syntrophin; exercise; brain; tadalafil (Cialis®); sildenafil citrate (Viagra®); muscular dystrophy; neuronal nitric oxide synthase (nNOS); two-hit hypothesis (two-hit theory) dystrophin; dystrophin-glycoprotein complex (DGC); syntrophin; exercise; brain; tadalafil (Cialis®); sildenafil citrate (Viagra®); muscular dystrophy; neuronal nitric oxide synthase (nNOS); two-hit hypothesis (two-hit theory)
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. (CC BY 4.0).

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Nichols, B.; Takeda, S.; Yokota, T. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains. Brain Sci. 2015, 5, 275-298.

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