Elucidating the Epigenetic and Protein Interaction Landscapes in Amyotrophic Lateral Sclerosis: An Integrated Bioinformatics Analysis

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness and paralysis. Understanding the molecular basis of ALS is crucial for the development of effective therapies. Objective: This study aims to explore the genetic and epigenetic underpinnings of ALS, focusing on the interplay between gene mutations, protein interactions, and epigenetic factors. Methods: We conducted an extensive analysis of key ALS-associated genes including TARDBP, SOD1, ANG, VAPB, and CHMP2B. We used computational tools to assess the functional consequences of identified mutations on neuronal health and explored DNA methylation patterns in gene promoters to investigate epigenetic regulation. Results: Our findings reveal that mutations in ALS-associated genes disrupt critical processes such as amyloid fibril formation and autophagy. We also identified altered DNA methylation patterns, suggesting a mechanism for changes in gene expression linked to ALS. Molecular docking studies highlighted Humulene and Buddledin C as compounds with high binding affinities to the SOD1 enzyme, suggesting their potential to mitigate hallmark features of ALS pathology such as SOD1 aggregation and oxidative stress. Conclusions: Our comprehensive analysis underscores the complexity of ALS pathogenesis, combining genetic, epigenetic, and proteomic approaches. The insights gained not only enhance our understanding of ALS but also pave the way for novel therapeutic strategies, highlighting the importance of integrated approaches in tackling this challenging neurodegenerative disease.