ArticleNature communications2019
mTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 121 citations in OpenAlex.
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- Aging-Related Changes in the Injury Response of the Peripheral Nervous System.Neuroscience bulletin · 2026Review
- Activation of α7nAChR reduces inflammation and apoptosis, promoting muscle regeneration through the AKT-FOXO1 pathway.Cell death and differentiation · 2026Article
- The role and mechanism of histone deacetylase in COPD.Molecular and cellular biochemistry · 2026Review
- CtBP1 sustains activity-dependent muscle properties and dampens synaptic, contractile and metabolic changes triggered by denervation.Skeletal muscle · 2026Article
- Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.JCI insight · 2026Article
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Botulinum toxin-induced masseter muscle atrophy is associated with impaired autophagic flux without signs of apoptosis in mice.Cell death discovery · 2026Article
- AKT Signaling Regulates Agrin-Mediated Acetylcholine Receptor Surface Density.Medicina (Kaunas, Lithuania) · 2026Article
- Acutely denervated muscle EVs reshape neuronal mitochondrial metabolism via retrograde signaling to rescue peripheral nerve injury.Cell reports. Medicine · 2026Article
- Conserved differential expression of DDX helicase and CPEB genes in skeletal muscles potentially influences neuromuscular junctions during aging: a computational analysis.Biogerontology · 2026Article
- Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.Current protein & peptide science · 2026Review
- Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.American journal of physiology. Cell physiology · 2025Article
- PRMT1 (protein arginine methyltransferase 1) is essential for neuromuscular junction and mitochondrial homeostasis via mitophagy regulation.Autophagy · 2025Article
- Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy.Nature metabolism · 2025Article
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- Response of UBR-box E3 ubiquitin ligases and protein quality control pathways to perturbations in protein synthesis and skeletal muscle size.bioRxiv : the preprint server for biology · 2025Article
- Hyperactivation of Transforming Growth Factor-β-Activated Kinase 1 Causes Skeletal Muscle Pathology Reminiscent of Inflammatory Myopathies.The American journal of pathology · 2025Article
- The multimodal transcriptional response of denervated skeletal muscle involves regulation ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Klotho Deficiency Promotes Skeletal Muscle Weakness and Is Associated with Impaired Motor Unit Connectivity.International journal of molecular sciences · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of innervation of skeletal muscle is a determinant event in several muscle diseases. Although several effectors have been identified, the pathways controlling the integrated muscle response to denervation remain largely unknown. Here, we demonstrate that PKB/Akt and mTORC1 play important roles in regulating muscle homeostasis and maintaining neuromuscular endplates after nerve injury. To allow dynamic changes in autophagy, mTORC1 activation must be tightly balanced following denervation. Acutely activating or inhibiting mTORC1 impairs autophagy regulation and alters homeostasis in denervated muscle. Importantly, PKB/Akt inhibition, conferred by sustained mTORC1 activation, abrogates denervation-induced synaptic remodeling and causes neuromuscular endplate degeneration. We establish that PKB/Akt activation promotes the nuclear import of HDAC4 and is thereby required for epigenetic changes and synaptic gene up-regulation upon denervation. Hence, our study unveils yet-unknown functions of PKB/Akt-mTORC1 signaling in the muscle response to nerve injury, with important implications for neuromuscular integrity in various pathological conditions.
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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.