Bioinformatic network analysis on the molecular interactions between Parkinson’s disease, alpha-synuclein, and infertility condition

Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition that is characterized by a progressive decline of neural pathways, and its pathology is associated with alpha-synuclein abnormalities. Currently, infertility affects about 10% of individuals of fertile age within the USA. Interestingly, an increased length of fertility is associated with a decreased incidence of PD. Our study utilized QIAGEN’s Ingenuity Pathway Analysis (IPA) to identify and analyze molecular pathways that affect the underlying connection between alpha-synuclein (SNCA)-associated Parkinson’s disease (PD) and infertility condition (IC). Furthermore, we explored nicotine’s potential as a therapeutic in preventing the exacerbation of IC in terms of SNCA. Results Although the connection between SNCA-related PD and IC is not well explored, the Qiagen Knowledge Base (QKB) showed an overlap of 12 distinct molecules between SNCA and IC. These molecular pathways were established by adding SNCA and IC to “Pathway Explorer” and establishing connections to distinct molecules including transcription regulators, cytokines, and other enzymes/proteins. The Molecule-Activity-Predictor (MAP) tool predicted that SNCA activation would lead to an exacerbation of PD and IC with the potential involvement of dihydrotestosterone (DHT) and caspases. Specifically, it was found that SNCA decreased MAPK8 expression, which led to a downstream upregulation of IC. Activation of nicotine within this overarching molecular network resulted in a downregulation in both PD pathology and IC. Conclusions Together, these findings reveal a possible connection between infertility condition and genes regularly associated with alpha-synuclein-related Parkinson’s disease while identifying nicotine as a potential therapeutic application. Graphical Abstract