Apr 9, 2020

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

BioRxiv : the Preprint Server for Biology
A. VermaVijayalakshmi Ravindranath

Abstract

We performed transcriptome analysis using RNAseq on substantia nigra pars compacta (SNpc) from mice after acute and chronic MPTP treatment and Parkinson's disease (PD) patients. Acute and chronic exposure to MPTP resulted in decreased expression of genes involved in sodium channel regulation. However, upregulation of pro-inflammatory pathways was seen after single dose but not after chronic MPTP treatment. Dopamine biosynthesis and synaptic vesicle recycling pathways were downregulated in PD patients and only after chronic MPTP treatment in mice. Genes essential for midbrain development and determination of dopaminergic phenotype such as, LMX1B, FOXA1, RSPO2, KLHL1, EBF3, PITX3, RGS4, ALDH1A1, RET, FOXA2, EN1, DLK1, GFRA1, LMX1A, NR4A2, GAP43, SNCA, PBX1 and GRB10 were downregulated in human PD and overexpression of LMX1B rescued MPP+ induced death in SH-SY5Y neurons. Downregulation of ensemble of genes involved in development and differentiation of dopaminergic neurons indicate their critical involvement in pathogenesis and progression of human PD.

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