A meta-analysis of transcriptomic profiles of Huntington’s disease patients

Description of robust transcriptomic alterations in Huntington's disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 6...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0253037-e0253037
Main Authors: Seefelder, Manuel, Kochanek, Stefan
Format: Article
Language:English
Subjects:
Alzheimer's disease
Analysis
Atrophy
Biology and life sciences
Biomedical materials
Brain
Cardiac muscle
Cdc42 protein
Cell division
Cognitive ability
Computer and Information Sciences
Gene therapy
Genes
Genetic aspects
Genetic transcription
Glucose tolerance
Human motion
Huntington's chorea
Huntington's disease
Huntingtons disease
Kinases
Medicine and Health Sciences
Meta-analysis
Metabolism
Muscles
Osteoporosis
Proteins
Signs and symptoms
Transcription
Transcription factors
Tumor necrosis factor-TNF
Weight loss
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Description of robust transcriptomic alterations in Huntington's disease is essential to identify targets for biochemical studies and drug development. We analysed publicly available transcriptome data from the brain and blood of 220 HD patients and 241 healthy controls and identified 737 and 661 genes with robustly altered mRNA levels in the brain and blood of HD patients, respectively. In the brain, a subnetwork of 320 genes strongly correlated with HD and was enriched in transport-related genes. Bioinformatical analysis of this subnetwork highlighted CDC42, PAK1, YWHAH, NFY, DLX1, HMGN3, and PRMT3. Moreover, we found that CREB1 can regulate 78.0% of genes whose mRNA levels correlated with HD in the blood of patients. Alterations in protein transport, metabolism, transcriptional regulation, and CDC42-mediated functions are likely central features of HD. Further our data substantiate the role of transcriptional regulators that have not been reported in the context of HD (e.g. DLX1, HMGN3 and PRMT3) and strongly suggest dysregulation of NFY and its target genes across tissues. A large proportion of the identified genes such as CDC42 were also altered in Parkinson's (PD) and Alzheimer's disease (AD). The observed dysregulation of CDC42 and YWHAH in samples from HD, AD and PD patients indicates that those genes and their upstream regulators may be interesting therapeutic targets.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0253037