ArticleThe Journal of biological chemistry2015
Inhibition of N-Methyl-D-aspartate-induced Retinal Neuronal Death by Polyarginine Peptides Is Linked to the Attenuation of Stress-induced Hyperpolarization of the Inner Mitochondrial Membrane Potential.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 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
- Intranasal Administration of an Arginine-Enriched Penetratin Peptide Confers Neuroprotection via Mitochondrial Functional Modulation in a Genetic Parkinson's Disease Model.CNS neuroscience & therapeutics · 2026Article
- 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
- Ionomycin Exhibits Potent and Selective Bactericidal Activity Against Clostridioides difficile Through Calcium-Dependent Membrane Disruption.MicrobiologyOpen · 2026Article
- The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024Review
- Structure-based design of peptidomimetic inhibitors of PSD-95 with improved affinity for the PDZ3 domain.FEBS letters · 2024Article
- The Structural Characteristics of Compounds Interacting with the Amantadine-Sensitive Drug Transport System at the Inner Blood-Retinal Barrier.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration.Life (Basel, Switzerland) · 2022Review
- 5-Lipoxygenase Inhibition Protects Retinal Pigment Epithelium from Sodium Iodate-Induced Ferroptosis and Prevents Retinal Degeneration.Oxidative medicine and cellular longevity · 2022Article
- Metformin Protects against NMDA-Induced Retinal Injury through the MEK/ERK Signaling Pathway in Rats.International journal of molecular sciences · 2021Article
- Arginine and Arginine-Rich Peptides as Modulators of Protein Aggregation and Cytotoxicity Associated With Alzheimer's Disease.Frontiers in molecular neuroscience · 2021Review
- Advances in D-Amino Acids in Neurological Research.International journal of molecular sciences · 2020Review
- Neuroprotective Cationic Arginine-Rich Peptides (CARPs): An Assessment of Their Clinical Safety.Drug safety · 2020Review
- Assessment of recombinant tissue plasminogen activator (rtPA) toxicity in cultured neural cells and subsequent treatment with poly-arginine peptide R18D.Neurochemical research · 2020Article
- Poly-Arginine Peptide-18 (R18) Reduces Brain Injury and Improves Functional Outcomes in a Nonhuman Primate Stroke Model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- In vitro cellular uptake and neuroprotective efficacy of poly-arginine-18 (R18) and poly-ornithine-18 (O18) peptides: critical role of arginine guanidinium head groups for neuroprotection.Molecular and cellular biochemistry · 2020Article
- pH-Responsive Polypeptide-Based Smart Nano-Carriers for Theranostic Applications.Molecules (Basel, Switzerland) · 2019Review
- Article
- Neuroprotective Agents in the Intensive Care Unit: -Neuroprotective Agents in ICU.Journal of pharmacopuncture · 2018Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
It is widely accepted that overactivation of NMDA receptors, resulting in calcium overload and consequent mitochondrial dysfunction in retinal ganglion neurons, plays a significant role in promoting neurodegenerative disorders such as glaucoma. Calcium has been shown to initiate a transient hyperpolarization of the mitochondrial membrane potential triggering a burst of reactive oxygen species leading to apoptosis. Strategies that enhance cell survival signaling pathways aimed at preventing this adverse hyperpolarization of the mitochondrial membrane potential may provide a novel therapeutic intervention in retinal disease. In the retina, brain-derived neurotrophic factor has been shown to be neuroprotective, and our group previously reported a PSD-95/PDZ-binding cyclic peptide (CN2097) that augments brain-derived neurotrophic factor-induced pro-survival signaling. Here, we examined the neuroprotective properties of CN2097 using an established retinal in vivo NMDA toxicity model. CN2097 completely attenuated NMDA-induced caspase 3-dependent and -independent cell death and PARP-1 activation pathways, blocked necrosis, and fully prevented the loss of long term ganglion cell viability. Although neuroprotection was partially dependent upon CN2097 binding to the PDZ domain of PSD-95, our results show that the polyarginine-rich transport moiety C-R(7), linked to the PDZ-PSD-95-binding cyclic peptide, was sufficient to mediate short and long term protection via a mitochondrial targeting mechanism. C-R(7) localized to mitochondria and was found to reduce mitochondrial respiration, mitochondrial membrane hyperpolarization, and the generation of reactive oxygen species, promoting survival of retinal neurons.
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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.