ArticleCell & bioscience2020
Delta opioid peptide [d-Ala2, d-Leu5] enkephalin confers neuroprotection by activating delta opioid receptor-AMPK-autophagy axis against global ischemia.
Article in Cell & bioscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The neuropeptide in ischemic brain injury: insights, challenges, and horizon of targeted interventions.Journal of translational medicine · 2026Pooled it
- Serendipitous Discovery of Short Peptides Dimethylammonium Salt Promoting Neural Differentiation.Journal of peptide science : an official publication of the European Peptide Society · 2026Article
- Delta-opioid receptor-mediated neural protection and regeneration.Neural regeneration research · 2026Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models.Cellular and molecular neurobiology · 2023Article
- Reinventing the Penumbra - the Emerging Clockwork of a Multi-modal Mechanistic Paradigm.Translational stroke research · 2023Review
- Delta Opioid Peptide Targets Brain Microvascular Endothelial Cells Reducing Apoptosis to Relieve Hypoxia-Ischemic/Reperfusion Injury.Pharmaceutics · 2022Article
- Protective potential of hydroxysafflor yellow A in cerebral ischemia and reperfusion injury: An overview of evidence from experimental studies.Frontiers in pharmacology · 2022Review
- Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy.Oxidative medicine and cellular longevity · 2022Review
- A novel link between silent information regulator 1 and autophagy in cerebral ischemia-reperfusion.Frontiers in neuroscience · 2022Review
- Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics.Pharmacology & therapeutics · 2021Review
- Article
- Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro.Journal of inflammation research · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIschemic stroke poses a severe risk to human health worldwide, and currently, clinical therapies for the disease are limited. Delta opioid receptor (DOR)-mediated neuroprotective effects against ischemia have attracted increasing attention in recent years. Our previous studies revealed that DOR activation by [d-Ala2, d-Leu5] enkephalin (DADLE), a selective DOR agonist, can promote hippocampal neuronal survival on day 3 after ischemia. However, the specific molecular and cellular mechanisms underlying the DOR-induced improvements in ischemic neuronal survival remain unclear.
resultsWe first detected the cytoprotective effects of DADLE in an oxygen-glucose deprivation/reperfusion (OGD/R) model and observed increased viability of OGD/R SH-SY5Y neuronal cells. We also evaluated changes in the DOR level following ischemia/reperfusion (I/R) injury and DADLE treatment and found that DADLE increased DOR levels after ischemia in vivo and vitro. The effects of DOR activation on postischemic autophagy were then investigated, and the results of the animal experiment showed that DOR activation by DADLE enhanced autophagy after ischemia, as indicated by elevated LC3 II/I levels and reduced P62 levels. Furthermore, the DOR-mediated protective effects on ischemic CA1 neurons were abolished by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, the results of the cell experiments revealed that DOR activation not only augmented autophagy after OGD/R injury but also alleviated autophagic flux dysfunction. The molecular pathway underlying DOR-mediated autophagy under ischemic conditions was subsequently studied, and the in vivo and vitro data showed that DOR activation elevated autophagy postischemia by triggering the AMPK/mTOR/ULK1 signaling pathway, while the addition of the AMPK inhibitor compound C eliminated the protective effects of DOR against I/R injury.
conclusionDADLE-evoked DOR activation enhanced neuronal autophagy through activating the AMPK/mTOR/ULK1 signaling pathway to improve neuronal survival and exert neuroprotective effects against ischemia.
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