ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Poly-arginine and arginine-rich peptides are neuroprotective in stroke models.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Efficacy of polyarginine peptides in the treatment of stroke: A systematic review and meta-analysis.Brain and behavior · 2023Pooled it
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Article
- Pharmacokinetics and Neuroprotective Efficacy of Poly-Arginine Peptide R18D in Sprague Dawley Rats Subjected to Transient Intraluminal Filament Middle Cerebral Artery Occlusion Stroke.CNS neuroscience & therapeutics · 2026Article
- Phytochemical-based nanomedicine as a promising therapeutic strategy for erectile dysfunction.Asian journal of andrology · 2026Review
- Back Again to the Future: A New Era for Cerebroprotection.Annals of neurology · 2026Review
- Cerebrospinal fluid profiles of targeted metabolomics on neurotransmitters in patients with post-neurosurgical bacterial meningitis.Frontiers in cellular and infection microbiology · 2025Article
- Membrane-Active Peptides and Their Potential Biomedical Application.Pharmaceutics · 2023Review
- Adsorption/Desorption of Cationic-Hydrophobic Peptides on Zwitterionic Lipid Bilayer Is Associated with the Possibility of Proton Transfer.Antibiotics (Basel, Switzerland) · 2023Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Assessment of the safety of the cationic arginine-rich peptides (CARPs) poly-arginine-18 (R18 and R18D) inBiochemistry and biophysics reports · 2022Article
- Effects of amyloid precursor protein peptide APP96-110, alone or with human mesenchymal stromal cells, on recovery after spinal cord injury.Neural regeneration research · 2022Article
- Positive allosteric regulation of PAC1-R up-regulates PAC1-R and its specific ligand PACAP.Acta biochimica et biophysica Sinica · 2022Article
- Interaction of Arginine-Rich Cell-Penetrating Peptides with an Artificial Neuronal Membrane.Cells · 2022Article
- Cerebral and Systemic Stress Parameters in Correlation with Jugulo-Arterial COJournal of clinical medicine · 2021Article
- Phase separation and toxicity of C9orf72 poly(PR) depends on alternate distribution of arginine.The Journal of cell biology · 2021Article
- Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke.International journal of molecular sciences · 2021Article
- Comparative Assessment of the Proteolytic Stability and Impact of Poly-Arginine Peptides R18 and R18D on Infarct Growth and Penumbral Tissue Preservation Following Middle Cerebral Artery Occlusion in the Sprague Dawley Rat.Neurochemical research · 2021Article
- Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer's Disease.Frontiers in molecular neuroscience · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using cortical neuronal cultures and glutamic acid excitotoxicity and oxygen-glucose deprivation (OGD) stroke models, we demonstrated that poly-arginine and arginine-rich cell-penetrating peptides (CPPs), are highly neuroprotective, with efficacy increasing with increasing arginine content, have the capacity to reduce glutamic acid-induced neuronal calcium influx and require heparan sulfate preotoglycan-mediated endocytosis to induce a neuroprotective effect. Furthermore, neuroprotection could be induced with immediate peptide treatment or treatment up to 2 to 4 hours before glutamic acid excitotoxicity or OGD, and with poly-arginine-9 (R9) when administered intravenously after stroke onset in a rat model. In contrast, the JNKI-1 peptide when fused to the (non-arginine) kFGF CPP, which does not rely on endocytosis for uptake, was not neuroprotective in the glutamic acid model; the kFGF peptide was also ineffective. Similarly, positively charged poly-lysine-10 (K10) and R9 fused to the negatively charged poly-glutamic acid-9 (E9) peptide (R9/E9) displayed minimal neuroprotection after excitotoxicity. These results indicate that peptide positive charge and arginine residues are critical for neuroprotection, and have led us to hypothesize that peptide-induced endocytic internalization of ion channels is a potential mechanism of action. The findings also question the mode of action of different neuroprotective peptides fused to arginine-rich CPPs.
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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.