Deciphering the molecular mechanism and crosstalk between Parkinson's disease and breast cancer through multi-omics and drug repurposing approach. (December 2022)

• Record Type: Journal Article
• Authors: Advani, Dia; Kumar, Pravir
• Is Part Of: Neuropeptides. Volume 96(2022)
• Publication Date: 2022-12
• Subjects: Multi-omics -- Parkinson's disease -- Breast cancer -- Molecular crosstalk -- Drug repurposing; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2022.102283
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstract: Epidemiological studies indicate a higher occurrence of breast cancer (BRCA) in patients with Parkinson's disease. However, the exact molecular mechanism is still not precise. Herein, we tested the hypothesis that this inverse comorbidity result from shared genetic and molecular processes. We conducted an integrated omics analysis to identify the common gene signatures associated with PD and BRCA. Secondly, several dysregulated biological processes in both indications were analyzed by functional enrichment methods, and significant overlapping processes were identified. To establish common regulatory mechanisms, information about transcription factors and miRNAs associated with both the disorders was extracted. Finally, disease-specific gene expression signatures were compared through LINCS L1000 analysis to identify potential repurposing drugs for PD. The potential repurposed drug candidates were then correlated with PD-specific gene signatures by Cmap analysis. In conclusion, this study highlights the shared genes, biological pathways and regulatory signatures associated with PD and BRCA with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was investigated in context with their comorbid associations. These findings could help to explain the complex molecular patterns of associations between PD and BRCA. Graphical abstract: Unlabelled Image Highlights: Transcriptional and post-transcriptional regulatory signatures are common in between PD and BRCA. Electron transport chain and oxidative phosphorylation as enriched pathways common between PD and BRCA. Raloxifene and tamoxifen as putative therapeutic agents in PD pathology. Raloxifene and tamoxifen alleviate PD pathogenesis through modulating estrogen receptor signaling. SERMs reverse neuroinflammation and modulate dopaminergic signaling in PD pathogenesis.