Unveiling the genes and pathways that are dysregulated in dopaminergic neurons during both familial and sporadic Parkinson’s disease

Abstract

AbstractIdentification of shared dysregulated genes and molecular mechanisms responsible for dopaminergic (DA) neuronal death in familial and sporadic forms of Parkinson’s disease (PD) can offer the potential for common therapies in both types of PD. The gene expression profiles of DA neurons with sporadic and familial PD backgrounds and healthy DA neurons were obtained from the Gene Expression Omnibus database. Overlapping differentially expressed genes and hub genes were identified. These genes were subjected to Gene Ontology and Reactome pathway enrichment analyses. The roles of a select few differentially expressed genes inC. elegansDA neuron health were assessed. 40 genes, including 12 hub genes, were found dysregulated in DA neurons with sporadic and familial PD. Altering the expression of some of these genes in wild-typeCaenorhabditis eleganspromoted DA neuron degeneration and function. The study unveils shared molecular mechanisms in DA neurons for familial and sporadic PD, potentially driving DA neuron degeneration. Understanding their roles may lead to targeted therapies, early detection, and intervention.In vivoexperiments support our hypothesis, suggesting the implication of these genes in PD neurodegeneration and neuroprotection.