ArticleCNS neuroscience & therapeutics2019
Urolithin A-activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo.
Article in CNS neuroscience & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 120 citations in OpenAlex.
- Urolithin A preserves renal perfusion and function and attenuates inflammasome-associated signaling in a translational porcine model of sepsis-induced acute kidney injury.Research square · 2026Article
- Autophagy activation by urolithin-a derivative UA-36 mitigates Friedreich's ataxia pathologies induced by frataxin deficiency.Molecular biomedicine · 2026Article
- Environmental enrichment as a mitochondria-targeting systems strategy across neurodegenerative diseases and retinal dystrophies.Frontiers in neuroscience · 2026Review
- Urolithin A enhances mitochondrial biogenesis-related markers and maximal respiratory capacity during C2C12 differentiation.Frontiers in cell and developmental biology · 2026Article
- Mitigating Pro-Inflammatory SASP and DAMP With Urolithin A: A Novel Senomorphic Strategy.Aging cell · 2025Article
- Microglial Autophagy and Mitophagy in Ischemic Stroke: From Dual Roles to Therapeutic Modulation.Biology · 2025Review
- Sepsis Induces Long-Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A.Journal of cachexia, sarcopenia and muscle · 2025Article
- Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges.Biomedicines · 2025Review
- The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease and future strategies for targeted therapy.European journal of medical research · 2025Review
- Effect of urolithin A on intracellular survival ofmSphere · 2025Article
- Urolithin as a Metabolite of Ellagitannins and Ellagic Acid from Fruits and Nuts Produced by the Gut Microbiota: Its Role on Non-Communicable Diseases.Current nutrition reports · 2025Review
- From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.Nutrition reviews · 2025Review
- Ellagic Acid: A Green Multi-Target Weapon That Reduces Oxidative Stress and Inflammation to Prevent and Improve the Condition of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Regulation of mitochondrial autophagy by lncRNA MALAT1 in sepsis-induced myocardial injury.European journal of medical research · 2024Article
- Urolithin A attenuates bupivacaine-induced neurotoxicity in SH-SY5Y cells by regulating the SIRT1-activated PI3K/AKT pathway.Histology and histopathology · 2024Article
- Urolithin C suppresses colorectal cancer progression via the AKT/mTOR pathway.Journal of natural medicines · 2024Article
- Urolithin A exerts anti-tumor effects on gastric cancer via activating autophagy-Hippo axis and modulating the gut microbiota.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Urolithin A Prevents Sleep-deprivation-induced Neuroinflammation and Mitochondrial Dysfunction in Young and Aged Mice.Molecular neurobiology · 2024Article
- The effects of urolithin A on poly I:C-induced microglial activation.Frontiers in cellular neuroscience · 2024Article
- Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia.International journal of molecular sciences · 2023Article
6 more citing papers are in PubMed but not listed here.
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
aimMitochondrial autophagy (mitophagy) clears damaged mitochondria and attenuates ischemic neuronal injury. Urolithin A (Uro-A) activates mitophagy in mammal cells and Caenorhabditis elegans. We explored neuroprotection of Uro-A against ischemic neuronal injury.
methodsMice were subjected to middle cerebral artery occlusion. The brain infarct and neurological deficit scores were measured. The N2a cells and primary cultured mice cortical neurons were subjected to oxygen-glucose deprivation and reperfusion (OGD/R). Uro-A was incubated during OGD/R, and cell injury was determined by MTT and LDH. Autophagosomes were visualized by transfecting mCherry-microtubule-associated protein 1 light chain 3 (LC3). The protein levels of LC3-II, p62, Translocase Of Inner Mitochondrial Membrane 23 (TIMM23), and cytochrome c oxidase subunit 4 isoform 1 (COX4I1) were detected by Western blot. The ER stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were determined by reverse transcription-polymerase chain reaction (RT-PCR).
resultsUrolithin A alleviated OGD/R-induced injury in N2a cells and neurons and reduced ischemic brain injury in mice. Uro-A reinforced ischemia-induced autophagy. Furthermore, Uro-A-conferred protection was abolished by 3-methyladenine, suggesting the requirement of autophagy for neuroprotection. However, mitophagy was not further activated by Uro-A. Instead, Uro-A attenuated OGD/R-induced ER stress, which was abolished by 3-methyladenosine. Additionally, neuroprotection was reversed by ER stress inducer.
conclusionUrolithin A protected against ischemic neuronal injury by reinforcing autophagy rather than mitophagy. Autophagy activation by Uro-A attenuated ischemic neuronal death by suppressing ER stress.
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