Transcriptome Network Biology Reveals the Neuroprotective Potential of Rosmarinic Acid Against Frontotemporal Dementia

Abstract

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterised by impaired behaviour and language. It affects individuals between 45 and 65 years of age. The present study aims to identify potential phytochemicals against target receptor of FTD. Transcriptome data analysis guided computer-aided drug design (CADD) was conducted to investigate molecular interactions between active phytochemicals present in Indian spices and differentially expressed genes. In present study, samples for patients with FTD were obtained from GEO dataset [GSE92340]. The samples were pre-processed followed by differential gene expression analysis using DESeq2. The patient sample was analyzed for 1882 upregulated genes. Hub gene out of DEGs was identified using CytoHubba Plugin of Cytoscape based on eleven parameters (Degree, Edge Percolated Component (EPC), Maximum Neighbourhood Component (MNC), Density of Maximum Neighbourhood Component (DMNC), Maximal Clique Centrality (MCC), Bottleneck, EcCentricity, Closeness, Radiality, Betweenness, and Stress). HDAC1 gene was identified as hub gene and key target in case of FTD. CADD pipeline was used to identify phytochemicals against HDAC1 gene. A list of eighty-one phytochemicals found in Indian spices was analyzed for their drug likeness abilities using molinspiration and toxicity prediction using ProTox-II, which identified twenty-three phytochemicals as safe drug-like compounds. PatchDock was employed to examine interactions between phytochemical compounds and HDAC1. Molecular interactions revealed rosmarinic acid derived from rosemary (Salvia rosmarinus) as the most effective drug for FTD having lowest ACE value of -395 kcal/mol. In conclusion, this study demonstrates essential role of HDAC1 in pathogenesis of FTD and demonstrates the neuroprotective potential of rosmarinic acid against FTD.