Parkinson's Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning.

Molecular Neurobiology
D M VargasF Klamt

Abstract

Parkinson's disease (PD) is among the most prevalent neurodegenerative diseases. Available evidences support the view of PD as a complex disease, being the outcome of interactions between genetic and environmental factors. In face of diagnosis and therapy challenges, and the elusive PD etiology, the use of alternative methodological approaches for the elucidation of the disease pathophysiological mechanisms and proposal of novel potential therapeutic interventions has become increasingly necessary. In the present study, we first reconstructed the transcriptional regulatory networks (TN), centered on transcription factors (TF), of two brain regions affected in PD, the substantia nigra pars compacta (SNc) and the frontal cortex (FCtx). Then, we used case-control studies data from these regions to identify TFs working as master regulators (MR) of the disease, based on region-specific TNs. Twenty-nine regulatory units enriched with differentially expressed genes were identified for the SNc, and twenty for the FCtx, all of which were considered MR candidates for PD. Three consensus MR candidates were found for SNc and FCtx, namely ATF2, SLC30A9, and ZFP69B. In order to search for novel potential therapeutic interventions, we used th...Continue Reading

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Citations

Aug 17, 2021·The Biochemical Journal·Amanda KowalczykKirill Kiselyov
Nov 18, 2021·Experimental Dermatology·Liat SamuelovEli Sprecher

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Datasets Mentioned

BETA
GSE60862
GSE49036
GSE28894

Methods Mentioned

BETA
ubiquitination
Immunoprecipitation Sequencing
ChIP-seq
GTPase
histone acetylation

Software Mentioned

ggplot2
Connectivity Map
R
clusterProfiler R
Gene Set Enrichment Analysis ( GSEA )
GSEA
Harmonizome
CMap
Rede R
Master Regulators Analysis ( MRA )

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