ReviewMolecular neurobiology2019
The ERK Pathway: Molecular Mechanisms and Treatment of Depression.
Review in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
143 citing papers in PubMed, 3 syntheses or guidelines pooled it, 263 citations in OpenAlex.
- Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.Translational psychiatry · 2026Pooled it
- Bibliometric and visual analysis in the field of electroacupuncture's analgesia and regulation on negative emotion from 2014 to 2024.Frontiers in neurology · 2025Pooled it
- Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.Molecular biology reports · 2021Pooled it
- Mechanisms of Selective Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: Cortico-Striatal Circuitry, Glutamatergic Dysregulation, and Neuroplastic Constraints.Molecular neurobiology · 2026Review
- ERK-dependent hyperexcitability of BLA neurons projecting to dCA3 underlies social dysfunction in a male mouse model of fragile X syndrome.EBioMedicine · 2026Article
- Temporal Interference Stimulation Enhances Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- KREO Prevents CUMS-Induced Depressive-Like Behavior via Modulation of the BDNF Signaling Pathway.Food science & nutrition · 2026Article
- Identification of susceptibility modules and genes through WGCNA and ceRNA network analysis in neuropathic pain-induced anxiodepression.Translational psychiatry · 2026Article
- Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling.Molecules and cells · 2026Article
- Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort.Molecular psychiatry · 2026Article
- The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice.Behavioral and brain functions : BBF · 2026Article
- Neuroimmune dysregulation and comorbidity mechanisms of major depressive disorder and migraine.BMC psychiatry · 2026Article
- Network pharmacology of cellular targets in major depressive disorder and differential mechanisms of fluoxetine, ketamine and esketamine.Computational and structural biotechnology journal · 2026Article
- Lurasidone ameliorates doxorubicin-induced chemobrain in male Wistar rats: involvement of the hippocampal and prefrontal cortex CREB/BDNF/Glt-1 axis and glutamate homeostasis.Frontiers in pharmacology · 2026Article
- Geniposide Improves Corticosterone-induced Toxicity in PC12 Cells through the NMDARs and BDNF Pathway.Cell biochemistry and biophysics · 2025Article
- Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.Translational psychiatry · 2025Article
- The Emerging Role of the DDAH Proteins in Psychiatric Disorders.Biological psychiatry global open science · 2025Review
- Acupuncture improves depressive-like behaviors in CUMS rats by modulating lateral habenula synaptic plasticity via the BDNF/ERK/mTOR pathway.Molecular brain · 2025Article
- Laminin-gamma2 promotes oral squamous cell carcinoma growth by activating the p-ERK/c-Myc signaling pathway.BMC oral health · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Major depressive disorder is a chronic debilitating mental illness. Its pathophysiology at cellular and molecular levels is incompletely understood. Increasing evidence supports a pivotal role of the mitogen-activated protein kinase (MAPK), in particular the extracellular signal-regulated kinase (ERK) subclass of MAPKs, in the pathogenesis, symptomatology, and treatment of depression. In humans and various chronic animal models of depression, the ERK signaling was significantly downregulated in the prefrontal cortex and hippocampus, two core areas implicated in depression. Inhibiting the ERK pathway in these areas caused depression-like behavior. A variety of antidepressants produced their behavioral effects in part via normalizing the downregulated ERK activity. In addition to ERK, the brain-derived neurotrophic factor (BDNF), an immediate upstream regulator of ERK, the cAMP response element-binding protein (CREB), a transcription factor downstream to ERK, and the MAPK phosphatase (MKP) are equally vulnerable to depression. While BDNF and CREB were reduced in their activity in the prefrontal cortex and hippocampus of depressed animals, MKP activity was enhanced in parallel. Chronic antidepressant treatment readily reversed these neurochemical changes. Thus, ERK signaling in the depression-implicated brain regions was disrupted during the development of depression, which contributes to the long-lasting and transcription-dependent neuroadaptations critical for enduring depression-like behavior and the therapeutic effect of antidepressants.
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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 Socratic graph.