ArticleJournal of the American Heart Association2021
New Cardiomyokine Reduces Myocardial Ischemia/Reperfusion Injury by PI3K-AKT Pathway Via a Putative KDEL-Receptor Binding.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Correlation between serum cerebral dopamine neurotrophic factor levels and severity of coronary artery lesions in acute myocardial infarction.Journal of thoracic disease · 2026Article
- Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Neurotrophic Factors: Emerging Biology and Therapeutic Applications for Cardiovascular Diseases.Metabolites · 2026Review
- Cerebral Dopamine Neurotrophic Factor (CDNF) Acts as a Trophic Factor Promoting Neuritogenesis in the Dorsal Root Ganglia (DRG) Neurons Through Activation of the PI3K Signaling Pathway.Journal of neurochemistry · 2025Article
- Preconditioning with acteoside ameliorates myocardial ischemia‑reperfusion injury by targeting HSP90AA1 and the PI3K/Akt signaling pathway.Molecular medicine reports · 2025Article
- CDNF Exerts Anxiolytic, Antidepressant-like, and Procognitive Effects and Modulates Serotonin Turnover and Neuroplasticity-Related Genes.International journal of molecular sciences · 2024Article
- Key subdomains of mesencephalic astrocyte-derived neurotrophic factor attenuate myocardial ischemia/reperfusion injury by JAK1/STAT1/NF-κB signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.Nature medicine · 2024Article
- The RISK pathway leading to mitochondria and cardioprotection: how everything started.Basic research in cardiology · 2023Review
- CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson's disease.Frontiers in psychiatry · 2023Review
- CDNF Interacts with ER Chaperones and Requires UPR Sensors to Promote Neuronal Survival.International journal of molecular sciences · 2022Article
- KDEL Receptors: Pathophysiological Functions, Therapeutic Options, and Biotechnological Opportunities.Biomedicines · 2022Review
- Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism.Molecular psychiatry · 2022Review
- CDNF and MANF regulate ER stress in a tissue-specific manner.Cellular and molecular life sciences : CMLS · 2022Article
- A Linarin Derivative Protects against Ischemia-Induced Neuronal Injury in Mice by Promoting Cerebral Blood Flow Recovery via KDELR-Dependent CSPG4 Activation.Oxidative medicine and cellular longevity · 2022Article
- Effects of Intermittent Hypoxia on Cytokine Expression Involved in Insulin Resistance.International journal of molecular sciences · 2021Review
- The Function of KDEL Receptors as UPR Genes in Disease.International journal of molecular sciences · 2021Review
- Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats.International journal of molecular sciences · 2021Article
- New Cardiomyokine Reduces Myocardial Ischemia/Reperfusion Injury by PI3K-AKT Pathway Via a Putative KDEL-Receptor Binding.Journal of the American Heart Association · 2021Article
- Isolation of Mitochondria From Fresh Mice Lung Tissue.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background CDNF (cerebral dopamine neurotrophic factor) belongs to a new family of neurotrophic factors that exert systemic beneficial effects beyond the brain. Little is known about the role of CDNF in the cardiac context. Herein we investigated the effects of CDNF under endoplasmic reticulum-stress conditions using cardiomyocytes (humans and mice) and isolated rat hearts, as well as in rats subjected to ischemia/reperfusion (I/R). Methods and Results We showed that CDNF is secreted by cardiomyocytes stressed by thapsigargin and by isolated hearts subjected to I/R. Recombinant CDNF (exoCDNF) protected human and mouse cardiomyocytes against endoplasmic reticulum stress and restored the calcium transient. In isolated hearts subjected to I/R, exoCDNF avoided mitochondrial impairment and reduced the infarct area to 19% when administered before ischemia and to 25% when administered at the beginning of reperfusion, compared with an infarct area of 42% in the untreated I/R group. This protection was completely abrogated by AKT (protein kinase B) inhibitor. Heptapeptides containing the KDEL sequence, which binds to the KDEL-R (KDEL receptor), abolished exoCDNF beneficial effects, suggesting the participation of KDEL-R in this cardioprotection. CDNF administered intraperitoneally to rats decreased the infarct area in an in vivo model of I/R (from an infarct area of ≈44% in the I/R group to an infarct area of ≈27%). Moreover, a shorter version of CDNF, which lacks the last 4 residues (CDNF-ΔKTEL) and thus allows CDNF binding to KDEL-R, presented no cardioprotective activity in isolated hearts. Conclusions This is the first study to propose CDNF as a new cardiomyokine that induces cardioprotection via KDEL receptor binding and PI3K/AKT activation.
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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.