In silico prospecting and analysis of natural phenolic compounds as potential inhibitors of the Glycogen Synthase Kinase 3-beta (GSK-3¿) protein with relevance for Alzheimer's disease.

• Grant number: 24/19902-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Regildo Márcio Gonçalves da Silva
• Grantee: Hugo Henrique Santos
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil

Abstract

Alzheimer's disease is a progressive neurodegenerative condition that affects millions of people worldwide, characterized by memory loss, cognitive decline, and behavioral changes, severely impacting patients' quality of life. One of the enzymes associated with the development and progression of the disease is Glycogen Synthase Kinase 3-beta (GSK-3¿), which plays a critical role in regulating cellular processes, including TAU protein phosphorylation and glucose metabolism. The hyperactivity of GSK-3¿ has been linked to the formation of neurofibrillary tangles and amyloid plaques, pathological features of Alzheimer's, making it a promising target for the development of inhibitory therapies. This project aims to prospect and analyze natural phenolic compounds, which possess antioxidant and neuroprotective activities, and explore their potential as GSK-3¿ inhibitors through in silico computational techniques. The methodology includes molecular docking, which will assess the compounds' affinity for the active site of GSK-3¿, quantitative structure-activity relationship (QSAR) analysis to identify structural patterns that promote inhibitory activity, and molecular dynamics to study the stability and conformation of the formed complexes. These studies are expected to enable the rational identification of new natural phenolic compounds as potential GSK-3¿ inhibitors, contributing to the development of novel therapies for Alzheimer's disease treatment."