The peptide-based drug cortexin inhibits brain caspase-8


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Although the peptide-based drug cortexin is used in clinical practice for a long time, the mechanisms of its action still remain poorly investigated. This underlies importance of elucidation of the molecular mechanisms responsible for the cortexin impact on brain functioning and identification of primary molecular targets. We hypothesized that the neuroprotective effects of cortexin may be associated with its ability to inhibit brain proteases involved in death of brain cells. Results of this study have shown that cortexin can effectively inhibit brain caspase-8. Other investigated proteases (caspase-1, -3, -9, cathepsin B, and calpain) demonstrated either lower sensitivity or lack of sensitivity to inhibition by cortexin. The original protease inhibitory activity of cortexin was also detected in a (more simple in composition) water-soluble fraction of peptides isolated from cortexin. Both cortexin and the isolated peptide fraction prevented glutamate-induced neuronal death in vitro. Thus the neuroprotective effect of cortexin may be associated with direct inhibition of the brain initiator caspase-8.

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A. Yakovlev

Institute of Higher Nervous Activity and Neurophysiology; Moscow Research and Clinical Center for Neuropsychiatry

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Email: al_yakovlev@rambler.ru
俄罗斯联邦, ul. Butlerova 5А, Moscow, 117485; ul. Donskaya 43, Moscow, 115419

A. Lyzhin

Department of Brain Research

Email: al_yakovlev@rambler.ru
俄罗斯联邦, per. Obukha 5, Moscow, 105064

L. Khaspekov

Department of Brain Research

Email: al_yakovlev@rambler.ru
俄罗斯联邦, per. Obukha 5, Moscow, 105064

A. Guekht

Moscow Research and Clinical Center for Neuropsychiatry; Department of Neurology, Neurosurgery, and Medical Genetics

Email: al_yakovlev@rambler.ru
俄罗斯联邦, ul. Donskaya 43, Moscow, 115419; ul. Ostrovitianova 1, Moscow, 117997

N. Gulyaeva

Institute of Higher Nervous Activity and Neurophysiology; Moscow Research and Clinical Center for Neuropsychiatry

Email: al_yakovlev@rambler.ru
俄罗斯联邦, ul. Butlerova 5А, Moscow, 117485; ul. Donskaya 43, Moscow, 115419

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