Aprepitant as plausible inhibitor of MAPK/ERK2 pathway to ameliorate neurological deficits post traumatic brain injury

Abstract

Traumatic Brain Injury (TBI) is an external insult to the brain which is a result of external forces due to the accidental injuries to the head. Even mild trauma to the brain leaves a significant damage that may further lead to the lifelong neurological complications. Till date there is no approved pharmacological therapy for treatment of neurological complications post TBI. Recently, scientific literature makes it evident that there are various signaling pathways which play an important role in the pathophysiology of the brain injuries. Targeting these signaling cascades which are known to cause damage to the nervous system and inhibiting them by a therapeutic agent might prove to be effective in decreasing neurological complications and potentially improving the quality of life of people post traumatic brain injury. MAPK/ERK2 signaling cascade seems to have role in neuroinflammation, apoptosis, neuronal excitotoxicity and demyelination after TBI that exacerbates the secondary injury and hamper the recovery after TBI. In the following paper, we hypothesized the neurotherapeutic potential of Aprepitant by inhibiting MAPK/ERK2 activation after TBI and we put forward the idea of repurposing this drug for TBI patients to combat neurological complications thereafter. Our hypothesis is backed by the in-silico studies. Molecular docking is a method of docking tiny ligands into macromolecular proteinsin order to score their complimentary values at thebinding sites. Docking studies shows good interaction between Aprepitant(ligand) and ERK2 protein and can be validated further by in vivo studies for its neurotherapeutical potential.