Essential Role and Therapeutic Approaches to Restore Dystrophin

Ravi Kiran^*
*Correspondence: Ravi Kiran, Department of Cardiac Anesthesiology Institute of Postgraduate Medical Education & Research, Kolkata, India, Email:

Opinion

Dystrophin is a rod-shaped cytoplasmic protein, and an vital part of a protein complex that interfaces the cytoskeleton of a muscle fiber to the encompassing extracellular grid through the cell layer. This complex is differently known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, for example, α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight 427 kDa.

Dystrophin is coded for by the DMD quality – the biggest known human gene, covering 2.4 megabases (0.08% of the human genome) at locus Xp21. The essential record in muscle measures around 2,100 kilobases and requires 16 hours to transcribe; the mature mRNA measures 14.0 kilobases. The 79-exon muscle transcript codes for a protein of 3685 amino acid residues.

Spontaneous or inherited mutations in the dystrophin gene can cause various types of muscular dystrophy, a disease characterized by moderate muscular wasting. The most widely recognized of these problems caused by genetic defects in dystrophin is Duchenne muscular dystrophy.

Dystrophin is a protein located between the sarcolemma and the outermost layer of myofilaments in the muscle fiber (myofiber). It is a strong protein, connecting actin fibers to other support proteins that dwell within surface of each muscle fiber's plasma membrane (sarcolemma). These help proteins within surface of the sarcolemma in turn links to two other consecutive proteins for a total of three linking proteins. The last connecting protein is joined to the fibrous endomysium of the whole muscle fiber. Dystrophin supports muscle fiber strength, and the absence of dystrophin reduces muscle stiffness, increments sarcolemmal deformability, and compromises the mechanical dependability of costameres and their associations with nearby myofibrils. This has been displayed in ongoing examinations where biomechanical properties of the sarcolemma and its connections through costameres to the contractile mechanical assembly were estimated and assists with forestalling muscle fiber injury. Development of flimsy fibers (actin) makes a pulling power on the extracellular connective tissue that in the end turns into the tendon of the muscle. The dystrophin associated protein complex also helps scaffold various signalling and channel proteins, implicating the DAPC in regulation of signalling processes.

Dystrophin deficiency has been absolutely settled as one of the root causes of the overall class of myopathies collectively referred to as muscular dystrophy. The deletions of one or a few exons of the dystrophin DMD gene reason Duchenne and Becker muscular dystrophies. The huge cytosolic protein was first distinguished in 1987 by Louis M. Kunkel later simultaneous works by Kunkel and Robert G. Worton to describe the transformed quality that causes Duchenne muscular dystrophy (DMD). No less than 9 disease causing transformations in this gene have been discovered.

Though its role in airway smooth muscle is not well established, late examination shows that dystrophin along with other subunits of dystrophin glycoprotein complex is related with phenotype maturation.

A variation of the DMD quality, which is on the X chromosome, named B006, to be an introgression from a Neanderthal modern human mating.