Genes critical for development and differentiation of dopaminergic neurons are downregulated in Parkinson's disease

We performed transcriptome analysis using RNAseq on substantia nigra pars compacta (SNpc) from mice after single exposure, 14 days after daily MPTP treatment and Parkinson9s disease (PD) patients. Single dose of MPTP resulted in downregulation of genes involved in sodium channel regulation, which was also observed after 14 days. Upregulation of pro-inflammatory pathways was seen after single dose but not after 14 days of MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated both in mice after 14 days of MPTP and PD patients. LMX1B, that is essential for midbrain development and determination of dopaminergic phenotype and other genes including FOXA1, RSPO2, KLHL1, EBF3, PITX3, RGS4, ALDH1A1, RET, FOXA2, EN1, DLK1, GFRA1, LMX1A, NR4A2, GAP43, SNCA, PBX1 and GRB10 were downregulated in human PD. Downregulation of ensemble of genes involved in development and differentiation of dopaminergic neurons indicate their critical involvement in pathogenesis and progression of human PD.