ArticleTranslational stroke research2020
Therapeutic Role of a Cysteine Precursor, OTC, in Ischemic Stroke Is Mediated by Improved Proteostasis in Mice.
Article in Translational stroke research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 70 citations in OpenAlex.
- Blocking FOXO4 confers neuroprotection against oxidative stress and ischemia-reperfusion caused neuronal injury.Journal of neuropathology and experimental neurology · 2026Article
- Disrupting FOXO4 function confers neuroprotection against oxidative stress and ischemia-reperfusion-caused neuronal injury.bioRxiv : the preprint server for biology · 2026Article
- Effect of the cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid onFrontiers in toxicology · 2026Article
- Proteasomal dysfunction in the mouse forebrain induces mitochondrial DNA release, cGAS-STING signaling activation, and necroptosis.Journal of neuropathology and experimental neurology · 2025Article
- Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders.Frontiers in immunology · 2025Review
- Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives.Frontiers in pharmacology · 2025Review
- Disulfidptosis: a new target for central nervous system disease therapy.Frontiers in neuroscience · 2025Review
- Ferroptosis in ischemic stroke: Animal models and mechanisms.Zoological research · 2024Review
- E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Mechanism of ferroptosis regulating ischemic stroke and pharmacologically inhibiting ferroptosis in treatment of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.Heliyon · 2024Review
- Effects of the New Thrombolytic Compound LT3001 on Acute Brain Tissue Damage After Focal Embolic Stroke in Rats.Translational stroke research · 2024Article
- A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke.Current protein & peptide science · 2024Review
- CircPTP4A2 Promotes Microglia Polarization in Cerebral Ischemic Stroke via miR-20b-5p/YTHDF1/TIMP2 Axis.Neuromolecular medicine · 2023Article
- Proteomic analysis to unravel the biochemical mechanisms triggered by Bacillus toyonensis SFC 500-1E under chromium(VI) and phenol stress.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Role of Ferroptosis in Stroke.Cellular and molecular neurobiology · 2023Review
- Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway.Frontiers in pharmacology · 2023Article
- Heat Shock-Induced Extracellular Vesicles Derived from Neural Stem Cells Confer Marked Neuroprotection Against Oxidative Stress and Amyloid-β-Caused Neurotoxicity.Molecular neurobiology · 2022Article
- Impact of Cardiovascular Diseases on Ischemic Stroke Outcomes.Journal of integrative neuroscience · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Oxidative stress aggravates brain injury following ischemia/reperfusion (I/R). We previously showed that ubiquilin-1 (Ubqln1), a ubiquitin-like protein, improves proteostasis and protects brains against oxidative stress and I/R-induced brain injury. Here, we demonstrate that a small molecule compound, L-2-oxothiazolidine-4-carboxylic acid (OTC) that functions as a precursor of cysteine, upregulated Ubqln1 and protected cells against oxygen-glucose deprivation-induced cell death in neuronal cultures. Further, the administration of OTC either at 1 h prior to ischemia or 3 h after the reperfusion significantly reduced brain infarct injury and improved behavioral outcomes in a stroke model. Administration of OTC also increased glutathione (GSH) level and decreased superoxide production, oxidized protein, and neuroinflammation levels in the penumbral cortex after I/R in the stroke mice. Furthermore, I/R reduced both Ubqln1 and the glutathione S-transferase protein levels, whereas OTC treatment restored both protein levels, which was associated with reduced ubiquitin-conjugated protein level. Interestingly, in the Ubqln1 knockout (KO) mice, OTC treatment showed reduced neuroprotection and increased ubiquitin-conjugated protein level when compared to the similarly treated non-KO mice following I/R, suggesting that OTC-medicated neuroprotection is, at least partially, Ubqln1-dependent. Thus, OTC is a potential therapeutic agent for stroke and possibly for other neurological disorders and its neuroprotection involves enhanced proteostasis.
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