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| Status |
Public on Apr 27, 2024 |
| Title |
Effects of dichloroacetate on transcriptional networks in rat Schwann cells and primary sensory neurons |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Peripheral neuropathy (PN) is a debilitating side effect of many pharmaceutical agents and is among the most common reasons why patients stop their treatment early. Dichloroacetate (DCA) is a therapeutic drug that inhibits the pyruvate dehydrogenase complex (PDC), thereby modulating metabolic flux in cells. Despite success in improving outcomes of disease, reversible PN has been the single factor limiting the therapeutic potential for DCA. As a result, clinical trials for the drug have been halted prematurely. Establishing toxicity pathways in cells of the peripheral nervous system (PNS) that are involved in DCA-induced PN would provide new opportunities to intervene and mitigate adverse side effects associated with DCA. We investigated the molecular mechanisms underlying DCA-induced injury to both glial and neuronal cells. It was hypothesized that SCs would show activated transcriptional responses associated with oxidative damage and apoptosis at therapeutic doses while these responses will be absent or reduced in DRGs. Experiments were expected to pinpoint molecular mechanisms underlying DCA-induced neurotoxicity, and to reveal the window of therapeutic intervention to reduce side effects associated with DCA in clinical settings.
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| Overall design |
RNA-seq profiling of dichloroacetate on transcriptional networks in rat Schwann cells and primary sensory neurons
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| Contributor(s) |
Martyniuk C |
| Citation missing |
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| Submission date |
Nov 26, 2022 |
| Last update date |
Apr 27, 2024 |
| Contact name |
Christopher Martyniuk |
| E-mail(s) |
cmartyn@ufl.edu
|
| Phone |
3523173905
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| Organization name |
University of Florida
|
| Street address |
8891 SW 79th Avenue
|
| City |
Gainesville |
| State/province |
FL |
| ZIP/Postal code |
32608 |
| Country |
USA |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA905669 |
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