ArticleFree radical biology & medicine2016
Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- The Transcriptomic and Proteomic Molecular Signatures of Equine Multiple-System Neuropathy (Grass Sickness).Cells · 2026Article
- Effect of clodronate on gene expression in the peripheral blood of horses.Journal of veterinary pharmacology and therapeutics · 2024Article
- Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses.Genes · 2021Article
- Increased α-tocopherol metabolism in horses with equine neuroaxonal dystrophy.Journal of veterinary internal medicine · 2021Article
- Oxidized LDLs as Signaling Molecules.Antioxidants (Basel, Switzerland) · 2021Review
- Article
- Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency.iScience · 2019Article
- Previously Identified Genetic Variants inGenes · 2019Article
- Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis.Journal of veterinary internal medicine · 2019Article
- Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways.Physiological genomics · 2018Article
- Assessment of Altered Cholesterol Homeostasis by Xenobiotics Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.Current protocols in toxicology · 2018Article
- Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.Journal of veterinary internal medicine · 2018Article
- A Missense Mutation in the Vacuolar Protein Sorting 11 (G3 (Bethesda, Md.) · 2018Article
- An innate immune response and altered nuclear receptor activation defines the spinal cord transcriptome during alpha-tocopherol deficiency in Ttpa-null mice.Free radical biology & medicine · 2018Article
- A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses.Skeletal muscle · 2018Article
- Equine degenerative myeloencephalopathy: prevalence, impact, and management.Veterinary medicine (Auckland, N.Z.) · 2018Review
- Article
- Tissue resolved, gene structure refined equine transcriptome.BMC genomics · 2017Article
- Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy.Journal of veterinary internal medicineArticle
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration.
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