Asian Journal of Research in Biochemistry

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual death of neurons over time. In addition, the complexity of the disease's molecular mechanisms and the limitations of effective treatments pose significant challenges. In this study, we proposed drug targets by employing an integrative bioinformatics methodology that combines differential gene expression analysis, functional enrichment, protein-protein interaction network construction methods, cell type-specific expression profiling, and molecular docking. The comparison of AD and unaffected brain samples shows that the differentially expressed genes (DEGs) are mainly involved in synaptic signalling, neuroinflammation, and immune regulation pathways. Taking these genes as seeds and developing neighbours in the PPI network gave rise to a cluster of genes with the highest condition specificity scores. Among the hub genes identified by network analysis were neuronal genes (NEUROD6, CBLN4) and immune/stress-related genes (C4A, VGF, FKBP5). Immune dysregulation and neuronal dysfunction in AD are closely intertwined. Among the co-chaperones involved in glucocorticoid signalling and immune modulation, FKBP5 was identified as a key hub. Moreover, it was shown to be predominantly expressed in glial cells. Molecular docking with FKBP5 showed that this protein can bind naturally with many drugs already in clinical use, such as Donepezil and Curcumin. Hence, these data mark FKBP5 as a potential drug target and, at the same time, emphasize the significance of the combined analysis of transcriptomes, networks, and 3D structures for identifying new molecular mechanisms of AD.