Regulation of neuronal repair and regeneration through inhibition of oligodendrocyte myelin glycoprotein (OMgp)

Abstract

The inability of neural cells to regenerate themselves after an injury represents the major difference between neural cells and other cells of the body. Various factors are responsible for this, as the expression of myelin-derived inhibitors of axonal outgrowth such as neurite outgrowth inhibitor (Nogo), myelin-associated growth factor, and oligodendrocyte-myelin glycoprotein (OMgp) hinder the central nervous system (CNS) axons to recover properly and inhibit the neuron regeneration. The patient with spinal cord injury can even permanently lose their function due to the inability of axons to regenerate. However, their role in neural regeneration in vivo is not known completely. During the study, we found that once CNS gets injured, the axon growth inhibitor OMgp binds to the Nogo-66 Receptor 1 (NgR1) which in turn restricts the normal functioning of CNS. Considering the OMgp as the target protein, two flavonoid libraries (curcumin and piperine) were screened against it to get potential inhibitors. The effectiveness of the ligands was first screened by three-tier structure-based virtual screening by Glide, Schrödinger. Based on the docking score, the best-docked compounds were taken for absorption, distribution, metabolism, and excretion analysis and the top two complexes from each library were chosen for simulation studies. Flavonoid ligands showed a much better binding affinity when compared with already known inhibitors Riluzole and Minocycline. To date, no natural inhibitors are known for OMgp. Hence, this study can provide novel insight for upcoming research in this area.

Communicated by Ramaswamy H. Sarma

Keywords:

• OMgp
• neural regeneration
• curcumin
• piperine
• riluzole
• minocycline

Acknowledgements

Authors are grateful to Director, Indian Institute of Information Technology, Allahabad, India for providing facilities for research and thankful to Ministry of Education, India for providing research fellowship.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Funding is provided by Science and Engineering Research Borad (SERB), DST, India (Project No: EEQ/2018/000486).