Stilbostemin C as a Potential Candidate for Therapeutic Targeting of Rab3b Protein in Countering Alzheimers

Abstract

Alzheimer’s disease (AD), the most common form of dementia, affects more than 20 million individuals globally. One of the main mechanisms driving the emergence of neurodegenerative illnesses, including AD, is dysfunction in neuronal autophagy. Autophagy is the only route for organelle turnover in cells and is crucial for breaking down aggregated and normal proteins, especially in stressful or injured situations [1]. The endocannabinoid system, the mTOR pathway, neuroinflammation, and the metabolism of A$\beta$ and tau protein are all important aspects of autophagy that may all work together to mediate its impact on AD [2]. As a result, drugs that target autophagy may lead to the development of novel therapeutic strategies for the treatment of AD. Tau protein tangles inside of cells and amyloid-$\beta$ containing neuritic plaques are two features of Alzheimer’s disease (AD). This kind of pathology demonstrates unequivocally that AD compromises the systems of neuronal housekeeping and protein quality regulation. Growing data suggest that autophagosome-lysosomal degradation can be hindered, which could interfere with the processing of A$\beta$ plaques and cause AD pathogenesis. The GEO datasets provide publicly available gene expression and clinical data on AD patients to study the prognosis of patient death rates and thereby identify AD biomarkers. In this study, we used the GDC data portal to analyze linked genes with clinical data to determine the most significant AD genes using functional enrichment analysis and protein-protein interaction (PPI). In order to distinguish the genes with different expression levels between the mutant and normal groups, we identified differential expression genes (DEGs). RAB3B, a member of the small GTP-binding protein RAB family that is involved in cell autophagy, is being used. There are several potential mechanisms that could inhibit the function of the RAB3B protein interactome and thus impair autophagy and promote AD pathology. Furthermore, we used the GDC Data Portal to estimate their significance in AD. A natural substance called Stilbostemin C might be evaluated as a therapy option. For a better understanding of the interactions between the bioactive substances and the RAB3B protein, molecular docking research was performed. According to the molecular docking analysis, Stilbostemin C has a stronger affinity for RAB3B. The ADME/T study also revealed the potential of Stilbostemin C for further research.