RESUMEN
Previous studies suggested the pharmacological potential of rat hemopressin (PVNFKFLSH) and its shorter synthetic peptide NFKF, to protect from pilocarpine-induced seizures in mice. Orally administered NFKF was shown to be hundred times more potent than cannabidiol in delaying the first seizure induced by pilocarpine in mice. Here, using an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis we have shown that C57BL/6 J mice orally administrated with NFKF (500 µg/kg) presented better EAE clinical scores and improved locomotor activity compared to saline administrated control mice. NFKF blocked the production of IL-1beta and IL-6, and has high scores binding cannabinoid type 2 receptors. Therefore, NFKF is an exciting new possibility to neurodegenerative diseases therapeutics.
Asunto(s)
Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/prevención & control , Hemoglobinas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Animales , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Hemoglobinas/química , Hemoglobinas/farmacología , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular/métodos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacología , RatasRESUMEN
Previous studies suggested the pharmacological potential of rat hemopressin (PVNFKFLSH) and its shorter synthetic peptide NFKF, to protect from pilocarpine-induced seizures in mice. Orally administered NFKF was shown to be hundred times more potent than cannabidiol in delaying the first seizure induced by pilocarpine in mice. Here, using an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis we have shown that C57BL/6J mice orally administrated with NFKF (500µg/kg) presented better EAE clinical scores and improved locomotor activity compared to saline administrated control mice. NFKF blocked the production of IL-1beta and IL-6, and has high scores binding cannabinoid type 2 receptors. Therefore, NFKF is an exciting new possibility to neurodegenerative diseases therapeutics.
RESUMEN
Previous studies suggested the pharmacological potential of rat hemopressin (PVNFKFLSH) and its shorter synthetic peptide NFKF, to protect from pilocarpine-induced seizures in mice. Orally administered NFKF was shown to be hundred times more potent than cannabidiol in delaying the first seizure induced by pilocarpine in mice. Here, using an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis we have shown that C57BL/6J mice orally administrated with NFKF (500µg/kg) presented better EAE clinical scores and improved locomotor activity compared to saline administrated control mice. NFKF blocked the production of IL-1beta and IL-6, and has high scores binding cannabinoid type 2 receptors. Therefore, NFKF is an exciting new possibility to neurodegenerative diseases therapeutics.
RESUMEN
Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides' biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development.
Asunto(s)
Descubrimiento de Drogas , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Oligopéptidos/farmacología , Animales , Humanos , Péptidos y Proteínas de Señalización Intracelular/química , Oligopéptidos/química , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides’ biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development.
RESUMEN
Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides’ biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development.