ArticleMolecular psychiatry2015
FGF-21, a novel metabolic regulator, has a robust neuroprotective role and is markedly elevated in neurons by mood stabilizers.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 97 citations in OpenAlex.
- FGF-FGFR Signaling in Parkinson's Disease: Mechanistic Links to Ferroptosis and Neuroprotection.Brain sciences · 2026Review
- Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms.Molecular neurobiology · 2025Review
- Evaluating the utility of growth differentiation factor 15 and fibroblast growth factor 21 as blood biomarkers for Rett syndrome.Scientific reports · 2025Article
- Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia.International journal of molecular sciences · 2025Article
- FGF21, a modulator of astrocyte reactivity, protects against ischemic brain injury through anti-inflammatory and neurotrophic pathways.Acta pharmacologica Sinica · 2025Article
- Cellular Stem Cell Therapy for Treating Traumatic Brain Injury: Strategies for Enhancement of Therapeutic Efficacy.Molecular neurobiology · 2025Review
- Genetically-engineered Salmonella typhimurium expressing FGF21 promotes neurological recovery in ischemic stroke via FGFR1/AMPK/mTOR pathway.Journal of neuroinflammation · 2025Article
- Intranasal administration of mesenchymal stem cells overexpressing FGF21 demonstrates therapeutic potential in experimental Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Genetically Predicted 3-Methoxytyrosine Mediates the Causal Association between Fibroblast Growth Factor 21 and Glioblastoma Multiforme.Journal of Cancer · 2025Article
- FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury.Frontiers in pharmacology · 2024Article
- Role of FGF21 in mediating the effect of phosphatidylcholine on GBM.Frontiers in oncology · 2024Article
- FGF21 modulates hippocampal cold-shock proteins and CA2-subregion proteins in neonatal mice with hypoxia-ischemia.Pediatric research · 2023Article
- Review
- Correction of Local Brain Temperature after Severe Brain Injury Using Hypothermia and Medical Microwave Radiometry (MWR) as Companion Diagnostics.Diagnostics (Basel, Switzerland) · 2023Article
- Decreased FGF19 and FGF21: possible underlying common pathogenic mechanism of metabolic and cognitive dysregulation in depression.Frontiers in neuroscience · 2023Article
- Increased serum fibroblast growth factor 21 levels are associated with adverse clinical outcomes after intracerebral hemorrhage.Frontiers in neuroscience · 2023Article
- Research progress of fibroblast growth factor in nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Article
- Diagnosis and Drug Prediction of Parkinson's Disease Based on Immune-Related Genes.Journal of molecular neuroscience : MN · 2022Article
- Serum Klotho and FGF23 Levels in Patients with Schizophrenia.Psychiatry and clinical psychopharmacology · 2022Article
- A Longitudinal Study of the Association between theInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.
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