ArticleCNS neuroscience & therapeutics2016
Cyclosporine A Treatment Abrogates Ischemia-Induced Neuronal Cell Death by Preserving Mitochondrial Integrity through Upregulation of the Parkinson's Disease-Associated Protein DJ-1.
Article in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Preclinical studies of mesenchymal stem cells transplantation in amyotrophic lateral sclerosis: a systemic review and metaanalysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Mitochondria as a therapeutic target in neurodegeneration caused by hypoxia and ischemia during the perinatal period.Pharmacological reports : PR · 2026Review
- Targeting DNA Damage and Repair Pathways in Cerebral Ischemic Stroke: From Bench to Bedside.Translational stroke research · 2026Review
- Hexokinase as a Central Hub in Neurodegeneration: From Metabolic Dysfunction to Therapeutic Innovation.Aging and disease · 2025Review
- Article
- Research progress of mitophagy in chronic cerebral ischemia.Frontiers in aging neuroscience · 2023Review
- The "mitochondrial stress responses": the "Dr. Jekyll and Mr. Hyde" of neuronal disorders.Neural regeneration research · 2022Review
- Neuroregeneration and functional recovery after stroke: advancing neural stem cell therapy toward clinical application.Neural regeneration research · 2021Article
- DJ-1 is indispensable for the S-nitrosylation of Parkin, which maintains function of mitochondria.Scientific reports · 2020Article
- Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition.Frontiers in pharmacology · 2020Review
- Enhancing Base Excision Repair of Mitochondrial DNA to Reduce Ischemic Injury Following Reperfusion.Translational stroke research · 2019Article
- The neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling.Apoptosis : an international journal on programmed cell death · 2019Article
- Mitochondria in Ischemic Stroke: New Insight and Implications.Aging and disease · 2018Review
- A Model of Perinatal Ischemic Stroke in the Rat: 20 Years Already and What Lessons?Frontiers in neurology · 2018Review
- Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy.Human molecular genetics · 2017Article
- Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms.Progress in neurobiology · 2017Review
- Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft Within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity Toward Blood-Brain Barrier Repair in Ischemic Stroke Rats.Stem cells (Dayton, Ohio) · 2017Article
- Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.Frontiers in neurology · 2017Article
- Oxytocin modulates GABAScientific reports · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aimsHypoxic-ischemia alters mitochondrial membrane potential (Δψm), respiratory-related enzymes, and mitochondrial DNA (mtDNA). Drugs acting on mitochondria, such as cyclosporine A (CsA), may reveal novel mitochondria-based cell death signaling targets for stroke. Our previous studies showed that Parkinson's disease-associated protein DJ-1 participates in the acute endogenous neuroprotection after stroke via mitochondrial pathway. DJ-1 was detected immediately after stroke and efficiently translocated into the mitochondria offering a new venue for developing treatment strategies against stroke. Here, we examined a molecular interaction between CsA and mitochondrial integrity in the in vitro acute stroke model of oxygen glucose deprivation/reperfusion (OGD/R) injury with emphasis on DJ-1.
methodsPrimary rat neuronal cells (PRNCs) were exposed to OGD/R injury and processed for immunocytochemistry, ELISA, and mitochondria-based molecular assays to reveal the role of DJ-1 in CsA modulation of mitochondrial integrity.
resultsAdministration of CsA before stroke onset (24 h pre-OGD/R) afforded significantly much more robust neuroprotective effects than when CsA was initiated after stroke (2 h post-OGD/R), revealing that CsA exerted neuroprotection in the early phase of ischemic stroke. CsA prevented the mitochondria-dependent cell death signaling pathway involved in cytochrome c (Cyt c)-induced intrinsic apoptotic process. CsA preserved cellular ATP content, but not hexokinase activity under hypoxic conditions. CsA prevented both mtDNA decrement and Δψm degradation after reperfusion, and enhanced secretion of DJ-1 in the mitochondria, coupled with reduced oxidative stress.
conclusionThese observations provided evidence that CsA maintained mitochondrial integrity likely via DJ-1 upregulation, supporting the concept that mitochondria-based treatments targeting the early phase of disease progression may prove beneficial in stroke.
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