Demystifying the influence of ferroptosis on Alzheimer’s and Parkinson’s diseases: A network and systems biology approach

Research into the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD) has spanned decades, unraveling deregulated signaling cascades in these diseases. Recently, the discovery of the link between ferroptosis and neurodegeneration has opened new avenues for neurodegenerative disease research. Despite this, the key players in the ferroptotic pathway potentially governing the progression of neurodegenerative disease remain unidentified. Thus, in the present study, we reconstructed two protein–protein interaction networks (PPINs) for AD and PD with their respective differentially expressed genes from post-mortem tissues and identified 21 highly connected clusters within the AD PPIN and 17 clusters within the PD PPIN. Then, we identified 8 ferroptotic transcription factors (FerrTFs) that regulate hub genes from the 7 deregulated clusters of AD and 6 FerrTFs from the 4 deregulated clusters of PD. Functional enrichment analysis of these clusters revealed impairment in important neurological functions. Finally, we identified 681 drugs with potential therapeutic effects against the 8 FerrTFs associated with AD and 633 drugs against the 6 FerrTFs linked to PD. In addition, 126 and 114 miRNAs might silence 7 and 5 FerrTFs against AD and PD, respectively. This exploratory study identifies potential markers of ferroptosis that could exacerbate these neurodegenerative diseases and also suggests possible therapeutic measures against them.