ArticleMolecular psychiatry2021
Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- The BDNF/TrkB/CREB signaling improves chronic stress-induced decreased ovarian reserve by inhibiting pyroptosis of granulosa cells and disorders of sex hormone secretion.Journal of ovarian research · 2026Article
- Synaptojanin-2-binding protein ameliorates oxidative stress, neuroinflammation and depression-like behaviors via SYNJ2/PIPRedox biology · 2026Article
- PDCD4: A Double-Edged Sword in Neurological Diseases.Molecular neurobiology · 2026Review
- Dysfunctional circular RNA network in major depressive disorder: dissecting the cell identity and potential clinical applications.Molecular psychiatry · 2026Review
- The effect of human-specific genetic variants on neuronal spinogenesis.Frontiers in genetics · 2026Review
- PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential.Molecular biology reports · 2025Review
- Vitamin B12 and Affective Disorders: A Focus on the Gut-Brain Axis.Alpha psychiatry · 2025Review
- Lifelong Impact of Prenatal Stress: Exacerbated Memory Impairments and Gene Expression Changes Under Adult Chronic Stress.Brain and behavior · 2025Article
- Baihe Dihuang Tang Exerts Antidepressant Effects via Modulation of MAOA-Mediated Serotonin Metabolism and Synaptic Plasticity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Activity-dependent phosphorylation of CDYL by CDK5 regulates fear memory in mice.Translational psychiatry · 2025Article
- Regulation of Apoptotic Pathways by MicroRNAs: A Therapeutic Strategy for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Environmental Enrichment Exposure Alleviates Geriatric Depressive-Like Symptoms through Regulating Neurogenesis and Neuroinflammation.Environment & health (Washington, D.C.) · 2025Article
- Identification and experimental validation of biomarkers associated with mitochondrial and programmed cell death in major depressive disorder.Frontiers in psychiatry · 2025Article
- Behavioral and Amygdala Biochemical Damage Induced by Alternating Mild Stress and Ethanol Intoxication in Adolescent Rats: Reversal by Argan Oil Treatment?International journal of molecular sciences · 2024Article
- PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Microglial Pdcd4 deficiency mitigates neuroinflammation-associated depression via facilitating Daxx mediated PPARγ/IL-10 signaling.Journal of neuroinflammation · 2024Article
- Programmed cell death 4 blocks autophagy and promotes dopaminergic neuronal injury in Parkinson's disease.Experimental and therapeutic medicine · 2024Article
- Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.Research (Washington, D.C.) · 2024Article
- D-mannose is a rapid inducer of ACSS2 to trigger rapid and long-lasting antidepressant responses through augmenting BDNF and TPH2 levels.Translational psychiatry · 2023Article
- HSPA12A controls cerebral lactate homeostasis to maintain hippocampal neurogenesis and mood stabilization.Translational psychiatry · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Brain-derived neurotrophic factor (BDNF) is a growth factor that plays vital roles in the neuron survival, growth, and neuroplasticity. Alteration to BDNF expression is associated with major depressive disorder. However, the BDNF translational machinery in depression remains unknown. Herein, we pointed that Pdcd4, a suppressor oncogene, acted as an endogenous inhibitor for the translation of BDNF, and selectively repressed the translation of BDNF splice variant IIc mRNA in an eIF4A-dependent manner. Chronic restraint stress (CRS) up-regulated Pdcd4 expression in hippocampus via decreasing mTORC1-mediated proteasomes degradation pathway, which resulted in the reduction of BDNF protein expression. Moreover, over-expression of Pdcd4 in the hippocampus triggered spontaneous depression-like behaviors under the non-stressed conditions in mice, while systemic or neuron-specific knockout of Pdcd4 reverses CRS-induced depression-like behaviors. Importantly, administration of Pdcd4 siRNA or an interfering peptide that interrupts the Pdcd4-eIF4A complex substantially promoted BDNF expression and rescued the behavioral disorders which were caused by CRS. Overall, we have discovered a previously unrecognized role of Pdcd4 in controlling BDNF mRNA translation, and provided a new method that boosting BDNF expression through blocking the function of Pdcd4 in depression, indicating that Pdcd4 might be a new potential target for depressive disorder therapy.
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Registered trials
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