Downregulation of the Ca ²⁺ sensor Synaptotagmin-1 ( SYT1 ) in Parkinson’s Disease: Insights from Gene Expression Profiling

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons and by the intracellular accumulation of alpha-synuclein, leading to motor and non-motor symptoms. Despite being a widely studied disease, so new mechanisms should be investigated as possible paths for future diagnostics and treatments in PD. Here, we performed an in silico analysis of the global gene expression of tissues from different brain regions (prefrontal area, putamen, and substantia nigra) in PD patients and controls, to demonstrate differentially expressed genes (DEGs). We analyzed the dataset series GSE20295 from GEO, which comprises GSE20168, GSE20291, and GSE20292. We identified 13 DEGs, all exhibiting downregulation in PD tissues compared to controls. Notably, the SYT1 (Synaptotagmin-1) gene demonstrated the lowest expression level and nearly the most significant adjusted p-value. SYT1 is implicated in calcium ion sensor activity, a functional domain showing substantial fold enrichment in our study. This gene encodes a protein pivotal for neurotransmitter release at synapses. We also found a significant role of calcium-related processes in PD pathology through GSEA, indicating an overall increase in their activity and a disruption in neurotransmitter release mechanisms mediated by Ca ²⁺ . Despite limited research on the correlation between SYT1 and PD to date, our findings suggest the SYT1 gene holds promise as a possible target for PD. Further investigations are needed to elucidate this association fully.