ArticlePloS one2013
A novel retro-inverso peptide inhibitor reduces amyloid deposition, oxidation and inflammation and stimulates neurogenesis in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Effect of a Fibroin Enzymatic Hydrolysate on Memory Improvement: A Placebo-Controlled, Double-Blind Study.Nutrients · 2018Trial
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- The Interplay of Inflammation and Gut-Microbiota Dysbiosis in Alzheimer's Disease: Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Podoplanin-positive cell-derived small extracellular vesicles contribute to cardiac amyloidosis after myocardial infarction.Cell reports · 2025Article
- Advancing Amyloid Aggregation Research: A Focus on Innovative Therapies, Molecular Modeling and Nano-Delivery Systems in Alzheimer's Disease.Current drug targets · 2025Review
- Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.Pharmaceutics · 2024Review
- A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Molecular Integrative Study on Inhibitory Effects of Pentapeptides on Polymerization and Cell Toxicity of Amyloid-β Peptide (1-42).Current issues in molecular biology · 2024Article
- Liposome nanoparticle conjugation and cell penetrating peptide sequences (CPPs) enhance the cellular delivery of the tau aggregation inhibitor RI-AG03.Journal of cellular and molecular medicine · 2024Article
- Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.International journal of nanomedicine · 2023Review
- Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges.Molecular pharmaceutics · 2022Review
- Molecular Mechanisms of Inhibition of Protein Amyloid Fibril Formation: Evidence and Perspectives Based on Kinetic Models.International journal of molecular sciences · 2022Review
- Blood-brain barrier: emerging trends on transport models and new-age strategies for therapeutics intervention against neurological disorders.Molecular brain · 2022Review
- Review
- Small Peptides for Inhibiting Serum Amyloid A Aggregation.ACS medicinal chemistry letters · 2021Article
- Recent Applications of Retro-Inverso Peptides.International journal of molecular sciences · 2021Review
- Gene therapy using Aβ variants for amyloid reduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Preclinical Marmoset Model for Targeting Chronic Inflammation as a Strategy to Prevent Alzheimer's Disease.Vaccines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previously, we have developed a retro-inverso peptide inhibitor (RI-OR2, rGffvlkGr) that blocks the in vitro formation and toxicity of the Aβ oligomers which are thought to be a cause of neurodegeneration and memory loss in Alzheimer's disease. We have now attached a retro-inverted version of the HIV protein transduction domain 'TAT' to RI-OR2 to target this new inhibitor (RI-OR2-TAT, Ac-rGffvlkGrrrrqrrkkrGy-NH(2)) into the brain. Following its peripheral injection, a fluorescein-labelled version of RI-OR2-TAT was found to cross the blood brain barrier and bind to the amyloid plaques and activated microglial cells present in the cerebral cortex of 17-months-old APPswe/PS1ΔE9 transgenic mice. Daily intraperitoneal injection of RI-OR2-TAT (at 100 nmol/kg) for 21 days into 10-months-old APPswe/PS1ΔE9 mice resulted in a 25% reduction (p<0.01) in the cerebral cortex of Aβ oligomer levels, a 32% reduction (p<0.0001) of β-amyloid plaque count, a 44% reduction (p<0.0001) in the numbers of activated microglial cells, and a 25% reduction (p<0.0001) in oxidative damage, while the number of young neurons in the dentate gyrus was increased by 210% (p<0.0001), all compared to control APPswe/PS1ΔE9 mice injected with vehicle (saline) alone. Our data suggest that oxidative damage, inflammation, and inhibition of neurogenesis are all a downstream consequence of Aβ aggregation, and identify a novel brain-penetrant retro-inverso peptide inhibitor of Aβ oligomer formation for further testing in humans as a potential disease-modifying treatment for Alzheimer's disease.
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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.