ArticleScientific reports2018
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Development of an HInternational journal of molecular sciences · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer.Clinical and experimental medicine · 2026Article
- Involvement of Proteasomal and Endoplasmic Reticulum Stress in Neurodegeneration After Global Brain Ischemia.Molecular neurobiology · 2023Article
- Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception.International journal of molecular sciences · 2023Review
- MDMX elevation by a novel Mdmx-p53 interaction inhibitor mitigates neuronal damage after ischemic stroke.Scientific reports · 2022Article
- Dose-Dependent Effects of Astaxanthin on Ischemia/Reperfusion Induced Brain Injury in MCAO Model Rat.Neurochemical research · 2022Article
- Targeting PI3K/Akt signal transduction for cancer therapy.Signal transduction and targeted therapy · 2021Review
- LncRNA MIAT enhances cerebral ischaemia/reperfusion injury in rat model via interacting with EGLN2 and reduces its ubiquitin-mediated degradation.Journal of cellular and molecular medicine · 2021Article
- Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- Protective Effects of Cannabidivarin and Cannabigerol on Cells of the Blood-Brain Barrier Under Ischemic Conditions.Cannabis and cannabinoid research · 2021Article
- Preconditioning-Activated AKT Controls Neuronal Tolerance to Ischemia through the MDM2-p53 Pathway.International journal of molecular sciences · 2021Article
- Neuroprotective Effects Against Cerebral Ischemic Injury Exerted by Dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 Axis.Molecular neurobiology · 2021Article
- Review
- Refocusing the Brain: New Approaches in Neuroprotection Against Ischemic Injury.Neurochemical research · 2021Review
- Differentially Expressed Genes and Their Clinical Significance in Ischaemic Stroke: An In-Silico Study.The Malaysian journal of medical sciences : MJMS · 2020Article
- Targeting MDM2 for novel molecular therapy: Beyond oncology.Medicinal research reviews · 2020Review
- Article
- The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.Translational stroke research · 2019Article
- Single-Nucleotide Polymorphism 309T>G in the MDM2 Promoter Determines Functional Outcome After Stroke.Stroke · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance.
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