Single-Cell Transcriptomics Uncovers Cellular Heterogeneity, Mechanisms, and Therapeutic Targets for Ferroptosis-Related Genes in Parkinson's Disease.

Neuronal ferroptosis is an important pathogenic mechanism of Parkinson's disease (PD). Therefore, it is of great significance to further explore the regulatory mechanisms of ferroptosis-related genes (FRGs) in PD. PD-related single-cell RNA sequencing datasets and transcriptome datasets were extracted from the Gene Expression Omnibus (GEO) database. Firstly, the core cells in PD-related single-cell RNA sequencing datasets were clustered, and main cell types were annotated. The differentially expressed genes (DEGs) between all cell types in PD and healthy control (HC) groups, as well as DEG2 of samples in PD and HC groups were identified, respectively. The key genes were obtained by intersecting the DEG1, DEGs2 and DE-FRGs. Based on them, the gene set enrichment analysis (GSEA) was adopted to study the functions of key genes. In this study, endothelial cells were defined as the key cells, and the functions of the DEGs in endothelial cells were associated with the NOD-like receptor signaling pathway. Screening the four key genes related to ferroptosis in PD, AKR1C3, HSPB1, MT1G, and PDK4, whose functions were related to synaptic transport, could deepen our understanding of the role of FRGs in PD and provide potential targets for future mechanistic studies.