title: [Peptide drug cortexin inhibits brain caspase-8].
abstract: Cortexin, a drug containing hydrolyzed brain peptides, has long been used in clinics, but the mechanisms of its action remain obscure. We have hypothesized that cortexin-related neuroprotection is associated with the ability of the drug to inhibit brain proteases. Cortexin effectively inhibited brain caspase-8, while its effects on caspase-1, -3, -9, cathepsin B and calpain were much less pronounced or absent. In addition, we isolated a peptide fraction from cortexin holding all the inhibitory capacity of the original drug, but with a much more simple composition. Both cortexin and its fraction prevented neuronal damage in a culture model of glutamate-induced cell death. Neuroprotective effect of Cortexin may be mediated by inhibition of the initiator caspase-8 in the brain.
authors.affiliation: Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia; Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Yakovlev
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Lyzhin
authors.affiliation: Research Center of Neurology, Moscow, Russia.
authors.forename: L G
authors.initials: LG
authors.lastname: Khaspekov
authors.affiliation: Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia.
authors.forename: A B
authors.initials: AB
authors.lastname: Guekht
authors.affiliation: Institute of Higher Nervous Activity and Neurophysiology, Moscow, Russia; Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russia; Russian National Research Medical University, Moscow, Russia.
authors.forename: N V
authors.initials: NV
authors.lastname: Gulyaeva
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression; D018698:Glutamic Acid / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D061251:Primary Cell Culture; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D011492:Protein Hydrolysates / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011480:Protease Inhibitors; D011492:Protein Hydrolysates; D018698:Glutamic Acid; D002154:Calpain; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002401:Cathepsin B; D020170:Caspase 1
keywords: brain; caspases; cortexin; peptides; proteases