INTERACTION OF ESEROLINE WITH BACE1: AN IN- SILICO APPROACH FOR ALZHEIMER’S THERAPY

Abstract

Alzheimer’s disease continues to be a challenging neurological disorder, primarily due to amyloid-ß plaques which accumulate and disrupt brain function. An enzyme that plays a central role in the development of these plaques is BACE1. It initiates the cleavage of APP, setting off a cascade of events. In my attempt to understand potential inhibitors, I ran a molecular docking study to observe how Eseroline, a derivative of physostigmine, might interact with BACE1. I used AutoDock 4.2 to run the simulations, and while the binding energy came out to roughly - 4.79 kcal/mol, which is not particularly strong, but it is definitely worth noting as it still suggested a degree of affinity. What stood out was the interaction with ARG43, a residue located in the pro-domain of BACE1. This region isn’t part of the mature catalytic site, so at first glance, it might not seem relevant but that’s precisely what makes it interesting. There's a chance that this kind of binding could impact how the protein matures or stabilizes, which isn’t something to overlook. These results are preliminary and entirely based on computational data, but they do raise some intriguing questions. Could Eseroline be influencing BACE1 in an indirect but meaningful way? Possibly. It’s something that deserves more attention if we're seriously exploring new angles for Alzheimer’s treatment.