NGS and Drug Development Pipeline for Alzheimers Disease

Abstract

Abstract: Alzheimer's disease is a form of dementia characterized by the gradual and irreversible loss of cognitive abilities, primarily affecting memory, thinking, and behaviour.Globally, there are more than 50 million people that suffer from Alzheimer's.Alzheimer's disease, a complex and devastating neurodegenerative disorder, represents a profound challenge to modern neuroscience and medicine. Defined by the accumulation of abnormal protein aggregates, such as beta-amyloid plaques and tau tangles, within the brain, it inexorably disrupts essential neuronal connections and communication. This relentless deterioration leads to a gradual deterioration of cognitive functions, memory loss, and ultimately, a profound loss of independence for afflicted individuals. Unravelling the intricate molecular and cellular mechanisms underlying Alzheimer's remains an urgent scientific endeavour, offering hope for novel treatments and preventive strategies to confront this formidable adversary of the human brain. In this study, the variability of the human γ-secretase, 5FN5protein sequence was compared and evaluated with the reference sequence using MMDB, BLAST, and COBALT. RasMol was utilized to identify the domain and function of the human γ secretase for the analysis of structural properties. Molecular docking was performed to study the interaction of 5FN5 molecule and the associated ligandusing PyMOL. In the computer-aided drug designing approach, molecular docking was performed for 5FN5 protein, and CB-Dock was used to find optimized conformations between 5FN5 protein and E2012 drug, resulting in the minimum energy that bound to a particular protein. E2012 was found to be the accurate drug ligand for the binding site of gamma secretase with docking score of –9, acting as a modulator for 5FN5 protein.