ArticlePloS one2015
β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Potential effects of β-hydroxy-β-methylbutyrate and exercise on brain aging and age-related disorders: implications for immunometabolic regulation and muscle-brain-immune crosstalk.Frontiers in aging neuroscience · 2026Review
- Nutritional intervention targeting muscle-brain axis in dementia continuum: from mechanisms to practice.Frontiers in nutrition · 2026Review
- International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB).Journal of the International Society of Sports Nutrition · 2025Review
- Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis.Investigative ophthalmology & visual science · 2025Article
- Formation of Neurointerfaces Based on Electrically Conductive Biopolymers by Two-Photon Polymerization Method.Polymers · 2025Article
- Flow-Induced Shear Stress Combined with Microtopography Inhibits the Differentiation of Neuro-2a Cells.Micromachines · 2025Article
- The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.Molecular neurobiology · 2025Review
- A Roadmap of Peptide-Based Materials in Neural Regeneration.Advanced healthcare materials · 2025Review
- Sodium Tungstate Promotes Neurite Outgrowth and Confers Neuroprotection in Neuro2a and SH-SY5Y Cells.International journal of molecular sciences · 2024Article
- Does β-Hydroxy-β-Methylbutyrate Have Any Potential to Support the Treatment of Duchenne Muscular Dystrophy in Humans and Animals?Biomedicines · 2023Review
- Nutraceuticals and Dietary Supplements for Older Adults with Long COVID-19.Clinics in geriatric medicine · 2022Review
- Effects of β-Hydroxy β-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents.Nutrients · 2022Article
- Eggshell Derived Europium Doped Hydroxyapatite Nanoparticles for Cell Imaging Application.Journal of fluorescence · 2021Article
- A Proton-Coupled Transport System for β-Hydroxy-β-Methylbutyrate (HMB) in Blood-Brain Barrier Endothelial Cell Line hCMEC/D3.Nutrients · 2021Article
- The long noncoding RNA Synage regulates synapse stability and neuronal function in the cerebellum.Cell death and differentiation · 2021Article
- Inhibition of RhoA/Rho kinase signaling pathway by fasudil protects against kainic acid-induced neurite injury.Brain and behavior · 2021Article
- Ethanolic Fruit Extract ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Differential regulation of mTORC1 activation by leucine and β-hydroxy-β-methylbutyrate in skeletal muscle of neonatal pigs.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways.Frontiers in molecular neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.
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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.