ArticleBMC cell biology2008
Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the beta-catenin-Ras-ERK-p21Cip/WAF1 pathway.
Article in BMC cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Prenatal valproic acid exposure in rodent models of autism: a systematic review of neurobehavioral physiological alterations.Frontiers in physiology · 2026Pooled it
- Multiomics analysis identifies VPA-induced changes in neural progenitor cells, ventricular-like regions, and cellular microenvironment in dorsal forebrain organoids.Molecular psychiatry · 2026Article
- A Comprehensive Review of the Genetic Etiology and Management of Orofacial Clefts.Pediatric discovery · 2026Review
- Stage-Dependent Disruptions in Neurogenesis and Neurotrophins' Production Following Prenatal and Postnatal Valproic Acid Exposure: Implications for Autism Spectrum Disorders.Cellular and molecular neurobiology · 2025Article
- Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan.EMBO molecular medicine · 2025Article
- The Differential Developmental Neurotoxicity of Valproic Acid on Anterior and Posterior Neural Induction of Human Pluripotent Stem Cells.International journal of stem cells · 2025Article
- Sex differences in clinical risk factors for Alzheimer's dementia patients with early-onset and late-onset.Frontiers in global women's health · 2025Article
- The effects of hesperidin on valproic acid-induced reduction in hippocampal neurogenesis through the antioxidant and apoptotic pathways in adult rats.Scientific reports · 2024Article
- BML-281 promotes neuronal differentiation by modulating Wnt/CaMolecular and cellular biochemistry · 2024Article
- Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.Current neuropharmacology · 2024Review
- Preparation and evaluation of controlled released implant containing mesoporous selenium nanoparticles loaded with curcumin in rats with spinal cord injury.Veterinary research forum : an international quarterly journal · 2024Article
- Understanding the role of AMPA receptors in autism: insights from circuit and synapse dysfunction.Frontiers in psychiatry · 2024Review
- Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway.BMC neuroscience · 2023Article
- Prenatal exposure to valproic acid alters Reelin, NGF expressing neuron architecture and impairs social interaction in their autistic-like phenotype male offspring.Experimental brain research · 2022Article
- A Small Molecule Promoting Neural Differentiation Suppresses Cancer Stem Cells in Colorectal Cancer.Biomedicines · 2022Article
- Human forebrain organoids reveal connections between valproic acid exposure and autism risk.Translational psychiatry · 2022Article
- Valproic acid enhances neurosphere formation in cultured rat embryonic cortical cells through TGFβ1 signaling.Journal of biomedical research · 2022Article
- Valproic acid exposure decreases neurogenic potential of outer radial glia in human brain organoids.Frontiers in molecular neuroscience · 2022Article
- Valproic acid and bladder healing: an experimental study in rats.Revista do Colegio Brasileiro de Cirurgioes · 2022Article
- Melatonin Ameliorates Valproic Acid-Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats.Oxidative medicine and cellular longevity · 2021Article
Corrections and comments
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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
backgroundValproic acid (VPA), a commonly used mood stabilizer that promotes neuronal differentiation, regulates multiple signaling pathways involving extracellular signal-regulated kinase (ERK) and glycogen synthase kinase3beta (GSK3beta). However, the mechanism by which VPA promotes differentiation is not understood.
resultsWe report here that 1 mM VPA simultaneously induces differentiation and reduces proliferation of basic fibroblast growth factor (bFGF)-treated embryonic day 14 (E14) rat cerebral cortex neural progenitor cells (NPCs). The effects of VPA on the regulation of differentiation and inhibition of proliferation occur via the ERK-p21Cip/WAF1 pathway. These effects, however, are not mediated by the pathway involving the epidermal growth factor receptor (EGFR) but via the pathway which stabilizes Ras through beta-catenin signaling. Stimulation of differentiation and inhibition of proliferation in NPCs by VPA occur independently and the beta-catenin-Ras-ERK-p21Cip/WAF1 pathway is involved in both processes. The independent regulation of differentiation and proliferation in NPCs by VPA was also demonstrated in vivo in the cerebral cortex of developing rat embryos.
conclusionWe propose that this mechanism of VPA action may contribute to an explanation of its anti-tumor and neuroprotective effects, as well as elucidate its role in the independent regulation of differentiation and inhibition of proliferation in the cerebral cortex of developing rat embryos.
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Registered trials
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