ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
- Article
- Therapeutic Potential of Sodium Butyrate in Neurological and Psychiatric Disorders.Molecular neurobiology · 2025Review
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Reduction of class I histone deacetylases ameliorates ER-mitochondria cross-talk in Alzheimer's disease.Aging cell · 2023Article
- Review
- What the Gut Tells the Brain-Is There a Link between Microbiota and Huntington's Disease?International journal of molecular sciences · 2023Review
- Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.Cell & bioscience · 2023Review
- Molecular Landscape of Tourette's Disorder.International journal of molecular sciences · 2023Article
- The role of short-chain fatty acids in central nervous system diseases.Molecular and cellular biochemistry · 2022Review
- Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives.International journal of molecular sciences · 2022Review
- Histone Modifications in Neurological Disorders.Advances in experimental medicine and biology · 2022Review
- Tryptophan metabolites in depression: Modulation by gut microbiota.Frontiers in behavioral neuroscience · 2022Review
- Analysis of Mitochondrial Dysfunction by Microplate Reader in hiPSC-Derived Neuronal Cell Models of Neurodegenerative Disorders.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions.Biomedicines · 2021Review
- New Avenues for the Treatment of Huntington's Disease.International journal of molecular sciences · 2021Review
- Article
- Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation.Developmental cell · 2021Article
- Oxygen Consumption Evaluation: An Important Indicator of Metabolic State, Cellular Function, and Cell Fate Along Neural Deregulation.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Age-Related Macular Degeneration: From Epigenetics to Therapeutic Implications.Advances in experimental medicine and biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We showed previously that the histone deacetylase inhibitors (HDACIs) trichostatin A and sodium butyrate (SB) ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work, we investigated the effect of HDACIs on the regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3). Exposure to dichloroacetate, an inhibitor of PDKs, increased mitochondrial respiration and decreased production of reactive oxygen species in mutant cells, emphasizing PDH as an interesting therapeutic target in HD. Treatment with SB and sodium phenylbutyrate, another HDACI, recovered cell viability and overall mitochondrial metabolism in mutant cells. Exposure to SB also suppressed hypoxia-inducible factor-1 (HIF-1α) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells. Concordantly, PDK3 knockdown improved mitochondrial function, emphasizing the role of PDK3 inactivation on the positive effects achieved by SB treatment. YAC128 mouse brain presented higher mRNA levels of PDK1-3 and PDH phosphorylation and decreased energy levels that were significantly ameliorated after SB treatment. Furthermore, enhanced motor learning and coordination were observed in SB-treated YAC128 mice. These results suggest that HDACIs, particularly SB, promote the activity of PDH in the HD brain, helping to counteract HD-related deficits in mitochondrial bioenergetics and motor function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.