ArticleThe Journal of biological chemistry2014
Forkhead transcription factor FOXO3a levels are increased in Huntington disease because of overactivated positive autofeedback loop.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- SKP2 regulates TERT independently of RUNX1/ETO in AML subtypes lacking the t(8,21) translocation via CDKN1B and RB phosphorylation states.Scientific reports · 2025Article
- FOXOs and their roles in acute and chronic neurological disorders.Frontiers in molecular biosciences · 2025Review
- Article
- Upregulation of HPV16E1 and E7 expression and FOXO3a mRNA downregulation in high-grade cervical neoplasia.PeerJ · 2024Article
- CNPY2 protects against ER stress and is expressed by corticostriatal neurons together with CTIP2 in a mouse model of Huntington's disease.Frontiers in molecular neuroscience · 2024Article
- FOXO family isoforms.Cell death & disease · 2023Review
- The regulatory role of lipophagy in central nervous system diseases.Cell death discovery · 2023Review
- Integrated Bioinformatics Analysis of Shared Genes, miRNA, Biological Pathways and Their Potential Role as Therapeutic Targets in Huntington's Disease Stages.International journal of molecular sciences · 2023Article
- Beneficial behavioral effects of chronic cerebral dopamine neurotrophic factor (CDNF) infusion in the N171-82Q transgenic model of Huntington's disease.Scientific reports · 2023Article
- Progressive transcriptional changes in metabolic genes and altered fatbody homeostasis in Drosophila model of Huntington's disease.Metabolic brain disease · 2022Article
- FOXO transcription factors as therapeutic targets in human diseases.Trends in pharmacological sciences · 2022Review
- Metabolism in Huntington's disease: a major contributor to pathology.Metabolic brain disease · 2022Review
- Article
- Therapeutic strategies targeting FOXO transcription factors.Nature reviews. Drug discovery · 2021Review
- Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington's disease.Scientific reports · 2020Article
- Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO.Molecular biology of the cell · 2020Article
- Review
- Dynamic Interaction of USP14 with the Chaperone HSC70 Mediates Crosstalk between the Proteasome, ER Signaling, and Autophagy.iScience · 2020Article
- Loss of KMT2D induces prostate cancer ROS-mediated DNA damage by suppressing the enhancer activity and DNA binding of antioxidant transcription factor FOXO3.Epigenetics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Huntington disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by an increased number of CAG repeats in the HTT gene coding for huntingtin. Decreased neurotrophic support and increased mitochondrial and excitotoxic stress have been reported in HD striatal and cortical neurons. The members of the class O forkhead (FOXO) transcription factor family, including FOXO3a, act as sensor proteins that are activated upon decreased survival signals and/or increased cellular stress. Using immunocytochemical screening in mouse striatal Hdh(7/7) (wild type), Hdh(7/109) (heterozygous for HD mutation), and Hdh(109/109) (homozygous for HD mutation) cells, we identified FOXO3a as a differentially regulated transcription factor in HD. We report increased nuclear FOXO3a levels in mutant Hdh cells. Additionally, we show that treatment with mitochondrial toxin 3-nitropropionic acid results in enhanced nuclear localization of FOXO3a in wild type Hdh(7/7) cells and in rat primary cortical neurons. Furthermore, mRNA levels of Foxo3a are increased in mutant Hdh cells compared with wild type cells and in 3-nitropropionic acid-treated primary neurons compared with untreated neurons. A similar increase was observed in the cortex of R6/2 mice and HD patient post-mortem caudate tissue compared with controls. Using chromatin immunoprecipitation and reporter assays, we demonstrate that FOXO3a regulates its own transcription by binding to the conserved response element in Foxo3a promoter. Altogether, the findings of this study suggest that FOXO3a levels are increased in HD cells as a result of overactive positive feedback loop.
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Registered trials
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