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Title: Gene expression data from HD mutant and wild type ST14A cells, differentiated for 24 hours and treated with vehicle (DMSO) or with 5µM MIND4      
dateReleased:
08-01-2013
description:
Activation of cellular responses through the NRF2/KEAP1/ARE pathway is a promising therapeutic strategy to counter neurodegeneration. The present study identified a novel lead compound, MIND4, which induces canonical NRF2-dependent responses and is protective in primary neurons, neuronal slice cultures and a Drosophila model of Huntington’s disease (HD). In accord with the known anti-inflammatory effects of NRF2 activation, MIND4 and its structural analog, potently repressed an expression of inflammatory markers in activated microglial cells. MIND4 treatment significantly reduced levels of TNF-alpha in the cortex of symptomatic HD mice, demonstrating the neuroprotective anti-inflammatory potential of NRF2 activator in the CNS. A high affinity reversible binding of MIND4 ligands to the NRF2 inhibitor, KEAP1, was identified by a docking model and confirmed by mechanistic studies, suggesting a novel approach to activating the NRF2 pathway. The results offer a new therapeutic path for HD and other human diseases. A total of 8 samples, HD mutant and wild type ST14A cells, stably expressing either a mutant expanded repeat (128Q) or wild type (26Q) 546 amino acid huntingtin fragment (a generous gift of E. Cattaneo) (Ehrlich et al., 2001)), 4 HD & 4 control, were used for drug treatment and array-based gene expression analysis. 4 samples, 2 HD and 2 Contol, were treated with 5µM MIND4 with each pair ran as replicates. The other 4 samples, 2 HD and 2 Contol, were treated with DMSO with each pair ran as replicates.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-49392
refinement:
raw
alternateIdentifiers:
49392
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Rattus norvegicus
ID:
A-AFFY-43
name:
Affymetrix GeneChip Rat Genome 230 2.0 [Rat230_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-49392/E-GEOD-49392.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-49392/E-GEOD-49392.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49392
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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