Unraveling the Core: Hub Genes Bridging Familial and Sporadic Parkinson's Disease

Parkinsons disease (PD), a neurodegenerative disorder characterized by dopaminergic (DA) neuron loss in the substantia nigra, manifests as familial (genetically linked) or idiopathic (sporadic) forms. Despite distinct etiologies, both subtypes converge on shared pathological mechanisms that remain poorly understood. This study focused on identifying "hub genes" that might drive DA neuron degeneration in familial and idiopathic PD. The gene expression data from three publicly available datasets were reanalyzed. These datasets included samples from DA neurons derived from postmortem brains and patient-derived induced pluripotent stem cells. Twelve hub genes were identified to be dysregulated across all three datasets. The hub genes were found to play vital roles in membrane trafficking and vesicle-mediated transport. NetworkAnalyst-based reconstruction linked these hub genes to various other diseases. Experimental validation in neurotoxin-induced SH-SY5Y cell models of PD confirmed significant changes in the mRNA levels of some of the hub genes. Crucially, silencing one of the hub genes in Caenorhabditis elegans promoted DA neuron degeneration. Our study identifies potential candidates as therapeutic targets for DA neuron degeneration in familial and idiopathic PD.