Interpreting the dynamic pathogenesis of Parkinson's disease by longitudinal blood transcriptome analysis

Achieving an improved understanding of the temporal sequence of factors involved in Parkinsons disease (PD) pathogenesis may accelerate drug discovery. In this study, we performed a longitudinal transcriptome analysis to identify associated genes underlying the pathogenesis of PD at three temporal phases. We firstly found that multiple initiator genes, which are related to processes of olfactory transduction and stem cell pluripotency, indicate PD risk to those subjects at the prodromal phase. And many facilitator genes involved in calcium signaling and stem cell pluripotency contribute to PD onset. We next identified 325 aggravator genes whose expression could lead to disease progression through damage to dopaminergic synapses and ferroptosis via an integrative analysis with DNA methylation. Last, we made a systematic comparison of gene expression patterns across PD development and accordingly provided candidate drugs at different phases in an attempt to prevent the neurodegeneration process.