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Omics data integration suggests a potential idiopathic Parkinson's disease signature.

Authors :
Zagare A
Preciat G
Nickels SL
Luo X
Monzel AS
Gomez-Giro G
Robertson G
Jaeger C
Sharif J
Koseki H
Diederich NJ
Glaab E
Fleming RMT
Schwamborn JC
Source :
Communications biology [Commun Biol] 2023 Nov 20; Vol. 6 (1), pp. 1179. Date of Electronic Publication: 2023 Nov 20.
Publication Year :
2023

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 reveal pyruvate, several amino acid 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.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
2399-3642
Volume :
6
Issue :
1
Database :
MEDLINE
Journal :
Communications biology
Publication Type :
Academic Journal
Accession number :
37985891
Full Text :
https://doi.org/10.1038/s42003-023-05548-w