ArticleProceedings of the National Academy of Sciences of the United States of America2008
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 323 citations in OpenAlex.
- ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.Molecular medicine (Cambridge, Mass.) · 2015Trial
- ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.Molecular medicine (Cambridge, Mass.) · 2013Trial
- Trial
- Erythropoietin in Tumor Immunity: Mechanistic Evidence, Clinical Cautions, and Translational Opportunities.Cancers · 2026Review
- Erythropoietin-derived Non-erythropoietic Peptides Conferring Oxidative Stress Resistance to Keratinocytes and Fibroblasts.Cell biochemistry and biophysics · 2026Article
- Peptide-Incorporated Biomaterials Promote Regeneration of Peripheral Nerve Injuries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Peptide-Based Approaches for Pain Relief and Healing in Wounds.International journal of molecular sciences · 2026Review
- An asymmetric tetrabody is a potent and efficacious agonist of the erythropoietin receptor in vitro and in vivo.Protein science : a publication of the Protein Society · 2025Article
- Multiple Mammalian Cytokines and Erythropoietin-Mimetic Peptides Protect Insect Neurons via Phylogenetically Conserved Cytokine Receptor-Like Factor 3 (CRLF3).Journal of neurochemistry · 2025Article
- A Novel Neuroprotective Derived Peptide of Erythropoietin Improved Cognitive Function in Vascular Dementia Mice.Molecular neurobiology · 2025Article
- Review
- Non-hematopoietic erythropoietin splice variant is produced in the diseased human brain and confers neuroprotection.Frontiers in cellular neuroscience · 2025Article
- Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.Current topics in medicinal chemistry · 2025Review
- Microglial EPOR Contribute to Sevoflurane-induced Developmental Fine Motor Deficits Through Synaptic Pruning in Mice.Neuroscience bulletin · 2024Article
- Co-treatment with erythropoietin derived HBSP and caspase-3 siRNA: A promising approach to prevent fibrosis after acute kidney injury.Journal of cellular and molecular medicine · 2024Article
- Neuroinflammation in Alzheimer's disease: insights from peripheral immune cells.Immunity & ageing : I & A · 2024Review
- NGF, EPO, and IGF-1 in the Male Reproductive System.Journal of clinical medicine · 2024Review
- Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke.CNS neuroscience & therapeutics · 2024Article
- Roles of macrophages in lupus nephritis.Frontiers in pharmacology · 2024Review
- Asialo-rhuEPO as a Potential Neuroprotectant for Ischemic Stroke Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.
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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.