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.

The efficacy and safety of animal-derived nootropics in cognitive disorders: Systematic review and meta-analysis

“…Actovegin is a highly purified extract of calf's blood comprising a mixture of over 200 biologically active components [8] . The exact mechanism of action of these agents is uncertain and pleiotropic effects including neuroprotection, regulation of neuronal metabolism, and neurotrophic activity have been postulated [ 7 , 9 , 10 ]. Direct and indirect effects of the nootropics on the cerebrovasculature have been described and some studies have suggested beneficial effects in stroke recovery.…”

“…Actovegin has been utilized for similar neurological conditions for nearly 50 years [ 8 , 9 ] and is licensed for use in Russia, Eastern European and Asian countries [8] . Cortexin is predominantly prescribed in Russia, where it used to treat a range of acute and chronic neurological disorders including stroke and cognitive impairment [ 10 , 13 ].…”

Postcovid Syndrome – The New Reality

“…Cortexin has been shown to produce effective and tissue-specifi c inhibition of caspase-8 activity in the brain. As proteases of the caspase family perform one of the key functions in neuron death in neurodegeneration, inhibition of caspase-8 can be regarded as a potentially possible mechanism of the neuroprotective action of the drug in vivo [48].…”

Molecular mechanisms of brain peptide-containing drugs: cortexin

“…В связи с тем, что протеазам семейства каспаз и кальпаина приписывают ключевую функцию в гибели нейронов при разных типах нейродегенерации, предположили, что среди пептидов кортексина могут находиться ингибиторы этих ферментов. Действительно, было показано [15], что кортексин эффективно и тканеспецифично ингибирует активность каспазы-8 головного мозга. Ингибирование каспаз-3, -8 и -9, а также катепсина В и кальпаина также отмечено, но оно было менее эффективным.…”

“…обладала нейропротективными свойствами in vitro. Ингибирование каспазы-8 может быть рассмотрено как один из потенциально возможных механизмов нейропротективного действия препарата in vivo [15].…”