ArticleEBioMedicine2019
Histone deacetylase 4 protects from denervation and skeletal muscle atrophy in a murine model of amyotrophic lateral sclerosis.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 57 citations in OpenAlex.
- Restoring Neural Homeostasis via Class II HDAC Modulation: Mechanistic Insights and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Protein arginine methyltransferases coordinate mitochondrial stress adaptation and neuromuscular function.Experimental & molecular medicine · 2026Review
- Neuromuscular Junction as a Molecular Target in Sarcopenia: Mechanisms, Therapeutic Strategies, and Future Directions.Molecular diagnosis & therapy · 2026Review
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- Review
- The Functions and Regulatory Mechanisms of Histone Modifications in Skeletal Muscle Development and Disease.International journal of molecular sciences · 2025Review
- Exploring epigenetic modifications as potential biomarkers and therapeutic targets in amyotrophic lateral sclerosis.Journal of neurology · 2025Review
- PROTAC-Mediated HDAC7 Protein Degradation Unveils Its Deacetylase-Independent Proinflammatory Function in Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epigenetics of Skeletal Muscle Atrophy.International journal of molecular sciences · 2024Review
- Review
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2024Review
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.Molecular neurobiology · 2023Review
- Epitranscriptomics as a New Layer of Regulation of Gene Expression in Skeletal Muscle: Known Functions and Future Perspectives.International journal of molecular sciences · 2023Review
- Sodium butyrate does not protect spinal motor neurons from AMPA-induced excitotoxic degeneration in vivo.Disease models & mechanisms · 2023Article
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- The epigenetic regulatory effect of histone acetylation and deacetylation on skeletal muscle metabolism-a review.Frontiers in physiology · 2023Review
- Sex and HDAC4 Differently Affect the Pathophysiology of Amyotrophic Lateral Sclerosis in SOD1-G93A Mice.International journal of molecular sciences · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistone deacetylase 4 (HDAC4) has been proposed as a target for Amyotrophic Lateral Sclerosis (ALS) because it mediates nerve-skeletal muscle interaction and since its expression in skeletal muscle correlates with the severity of the disease. However, our recent studies on the skeletal muscle response upon long-term denervation highlighted the importance of HDAC4 in maintaining muscle integrity.
methodsTo fully identify the yet uncharacterized HDAC4 functions in ALS, we genetically deleted HDAC4 in skeletal muscles of a mouse model of ALS. Body weight, skeletal muscle, innervation and spinal cord were analyzed over time by morphological and molecular analyses. Transcriptome analysis was also performed to delineate the signaling modulated by HDAC4 in skeletal muscle of a mouse model of ALS.
findingsHDAC4 deletion in skeletal muscle caused earlier ALS onset, characterized by body weight loss, muscle denervation and atrophy, and compromised muscle performance, although the main catabolic pathways were not activated. Transcriptome analysis identified the gene networks modulated by HDAC4 in ALS, revealing UCP1 as a top regulator that may be implicated in worsening ALS features.
interpretationHDAC4 plays an important role in preserving innervations and skeletal muscle in ALS, likely by modulating the UCP1 gene network. Our study highlights a possible risk in considering HDAC inhibitors for the treatment of ALS. FUND: This work was supported by FIRB grant (RBFR12BUMH) from Ministry of Education, Universities and Research, by Fondazione Veronesi, by Sapienza research project 2017 (RM11715C78539BD8) and Polish National Science Center grant (UMO-2016/21/B/NZ3/03638).
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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.