ArticleMolecular and cellular neurosciences2008
Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling.
Article in Molecular and cellular neurosciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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Who cites it
39 citing papers in PubMed, 88 citations in OpenAlex.
- Inflammatory macrophage-derived plasminogen activator inhibitor-1 exacerbates inflammation through efferocytosis inhibition.Cell death discovery · 2026Article
- Genetic Polymorphisms Associated with Lithium Response in Bipolar Disorder: An Integrative Review and In Silico Protein-Protein Interaction Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The crosstalk between CREB and PER2 mediates the transition between mania- and depression-like behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders.Nature communications · 2025Article
- Lithium rescues dendritic abnormalities in Ank3 deficiency models through the synergic effects of GSK3β and cyclic AMP signaling pathways.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders.medRxiv : the preprint server for health sciences · 2023Article
- Permissive effect of GSK3β on profibrogenic plasticity of renal tubular cells in progressive chronic kidney disease.Cell death & disease · 2021Article
- Effects of Long-Term Endurance Exercise and Lithium Treatment on Neuroprotective Factors in Hippocampus of Obese Rats.International journal of environmental research and public health · 2020Article
- The genetics of bipolar disorder.Molecular psychiatry · 2020Review
- Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis.Frontiers in physiology · 2019Article
- Activity-Independent Effects of CREB on Neuronal Survival and Differentiation during Mouse Cerebral Cortex Development.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Antifibrotic Actions of Peroxisome Proliferator-Activated Receptor γ Ligands in Corneal Fibroblasts Are Mediated by β-Catenin-Regulated Pathways.The American journal of pathology · 2017Article
- Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology.Frontiers in aging neuroscience · 2017Article
- Adenosine ABritish journal of pharmacology · 2016Article
- Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.PLoS genetics · 2016Article
- Inositol depletion, GSK3 inhibition and bipolar disorder.Future neurology · 2016Review
- The TGF-β pathway is activated by 5-fluorouracil treatment in drug resistant colorectal carcinoma cells.Oncotarget · 2016Article
- DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.Biological psychiatry · 2015Article
- Neuron membrane trafficking and protein kinases involved in autism and ADHD.International journal of molecular sciences · 2015Review
- Potential application of lithium in Parkinson's and other neurodegenerative diseases.Frontiers in neuroscience · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Smad proteins are intracellular transducers for transforming growth factor-beta (TGF-beta) signaling and play a critical role in differentiation, tissue repair and apoptosis of the central nervous system. Both TGF-beta and its regulated gene, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in the etiology and progression of neurodegenerative diseases and mood disorders. We previously reported that GSK-3beta protein depletion suppresses Smad3/4-dependent gene transcription and causes a reduction in PAI-1 expression. Here, we provide evidence that lithium, the drug for the treatment and prophylaxis of bipolar disorder, inhibits Smad-dependent signaling by regulating cAMP-protein kinase A (PKA), AKT-glycogen synthase kinase-3beta (GSK-3beta), and CRE-dependent signaling pathways in neuron-enriched cerebral cortical cultures of rats. We demonstrate that lithium-induced activation of these pathways inhibits Smad3/4-dependent gene transcription through an increase in pCREB(Ser133) protein levels, an enhanced interaction between pCREB(Ser133) and p300/CBP, which causes Smad3/4-p300/CBP complex disruption and transcriptional suppression of Smad3/4-dependent genes. Therapeutic implications of our findings are discussed.
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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.