Omics data integration suggests a potential idiopathic Parkinson’s disease signature#

Authors#

Alise Zagare, German Andres Preciat Gonzalez, Sarah Nickels, Xi Luo, Anna Sophia Monzel, Gemma Gomez-Giro, Graham Robertson, Christian Jäger, Jafar Sharif, Haruhiko Koseki, Nico Diederich, Enrico Glaab, Ronan M.T. Fleming, Jens Christian Schwamborn

Abstract#

The vast majority of Parkinson’s disease cases are idiopathic. Unclear etiology and multifactorial nature complicate the comprehension of disease pathogenesis. Identification of early transcriptomic and metabolic alterations consistent across different idiopathic Parkinson’s disease (IPD) patients might reveal the potential basis of increased dopaminergic neuron vulnerability and primary disease mechanisms. In this study, we combine systems biology and data integration approaches to identify differences in transcriptomic and metabolic signatures between IPD patient and healthy individual-derived midbrain neural precursor cells. Characterization of gene expression and metabolic modeling reveals pyruvate, several amino acids and lipid metabolism as the most dysregulated metabolic pathways in IPD neural precursors. Furthermore, we show that IPD neural precursors endure mitochondrial metabolism impairment and a reduced total NAD pool. Accordingly, we show that treatment with NAD precursors increases ATP yield hence demonstrating a potential to rescue early IPD-associated metabolic changes.