Abstract

A demyelinating sickness is any ailment of the nervous system in which the myelin casing of neurons is injured. This harm weakens the transmission of signals in the pretentious nerves. Demyelinating diseases, like multiple sclerosis (MS) and Charcot-Marie-Tooth (CMT) disease, are categorized on the basis of the scratch of the myelin covering around neurons, because of swelling and gliosis in the central nervous system (CNS) and peripheral nervous system (PNS), respectively. In this current research, an amalgam approach of comparative modeling and molecular docking pursued by inhibitor recognition and structure modeling was used. Existing treatments mark anti-inflammatory ways to hinder or slow disease sequence. The recognition of a means to improve axon myelination would present innovative remedial approaches to restrain and probably turn around disease progression. A computational ligand-target docking method was applied to investigate structural composites of the Leucine Rich Repeat and Ig Domain Containing 1 (LINGO1) with three ligands to understand the structural foundation of this protein goal specificity. The following ten residues were conserved for all the three ligands interaction LEU133, ILE134, Pro135, LEU136, ILE155, ILE157, LEU159, ASP160, TYR161, and MET162 which are present in Leucine Rich Repeat 3 and 4 domains. Therefore, these three ligands can be utilized as the potential inhibitors to prevent various neurological disorders and the axonal neuropathies especially the CMT disease. Docking analysis showed that the two important drugs which are widely used have the potential to block the Rho-Rock pathways. Here, we report inhibitors which showed maximum binding affinity for the three most important axonal regeneration inhibitors. However, further studies are required to find the applications of these drugs.

Key words: Demyelination, RTN4, CMT1A, spinal cord injury, ROCK inhibition, neurite growth inhibitors.

Abbreviation

LINGO1, Leucine rich repeat and Ig domain containing 1; MS, multiple sclerosis; MAG, myelin-associated glycoprotein; CMT, Charcot-Marie-Tooth disease; NgR, Nogo-66 receptor; SCI, spinal cord injury; MAIFs, myelin-associated inhibitory factors.