To elaborate a computational model of the role of melatonin in the pathogenesis and disrupted sleep in multiple sclerosis.

Melatonin, hormone of the pineal gland, exhibits immunomodulatory properties. T helper (Th) cells bear G-protein-coupled melatonin cell membrane receptors and, perhaps, melatonin nuclear receptors. The Th17 subset plays a key role in multiple sclerosis pathogenesis and Th17-mediated inflammation is characterized by neutrophil recruitment into the CNS and neurons killing.

The model was elaborated based on computational simulations that analyzed (1) activation of melatonin receptors; (2) the structure, composition, synthesis and physical-chemical properties of the melatonin; (3) the release of T helper cell type 1 (Th1) cytokines, such as interferon-γ (IFN-γ) and interleukin-2 (IL-2); (4) the stimulation of antibody-dependent cellular cytotoxicity; (5) the inflammatory cytokine production (including IL-12) from human monocytes and macrophages; (6) the melatonin-dependent regulation of Th17; (7) the regulation of the sleep-wake cycle and disease activity; (8) the role of the blood-brain barrier in multiple sclerosis. The model, computational simulations and analyzes of this scientific work were elaborated with the use of software: ACD/ChemSketch, Swiss-PdbViewer, ABCpred, BepiPred-2.0, ElliPro, DEseq, GOseq, FunRich, Cytoscape, BiNGO, PepSurf, AxonDeepSeg, AxonSeg, Computer-assisted Evaluation of Myelin formation (CEM), PyMol, ICM-Browser, Visual Molecular Dynamics (VMD), Cell Illustrator, C-ImmSim, Simmune, GENESIS, NEURON, NeuronStudio and ChemDraw.

The computational model of this work suggests that melatonin-dependent regulation of Th17 and balance of Th17/Treg is a possible mechanism for the development of multiple sclerosis. This model also suggests a relationship between melatonin, cytokines levels and blood brain barrier (BBB) disruption.

Understanding the relation between mechanisms of immune-mediated destruction of CNS components in MS and the role of melatonin in the pathogenesis promises to not only promote effective design of MS therapeutics, but also provides a broader understanding of immune-mediated diseases affecting the CNS.