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| Status |
Public on Aug 01, 2013 |
| 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 |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Thompson LM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jul 31, 2013 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Leslie Thompson |
| E-mail(s) |
lmthomps@uci.edu
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| Organization name |
University of California, Irvine
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| Street address |
Biological Sciences III
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| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92697 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (8)
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| GSM1198735 |
Wildtype ST14A Cells_5µM MIND4_Biological Replicate 1 |
| GSM1198736 |
Wildtype ST14A Cells_5µM MIND4_Biological Replicate 2 |
| GSM1198737 |
Wildtype ST14A Cells_DMSO_Biological Replicate 1 |
| GSM1198738 |
Wildtype ST14A Cells_DMSO_Biological Replicate 2 |
| GSM1198739 |
HD mutant ST14A Cells_5µM MIND4_Biological Replicate 1 |
| GSM1198740 |
HD mutant ST14A Cells_5µM MIND4_Biological Replicate 2 |
| GSM1198741 |
HD mutant ST14A Cells_DMSO_Biological Replicate 1 |
| GSM1198742 |
HD mutant ST14A Cells_DMSO_Biological Replicate 2 |
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| Relations |
| BioProject |
PRJNA213880 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49392_RAW.tar |
21.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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