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Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b

  • STRUCTURAL-FUNCTIONAL ANALYSIS OF BIOPOLYMERS AND THEIR COMPLEXES
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Abstract

Cortexin is a clinically approved cerebral cortex polypeptide complex in calves. The mechanism of cortexin action is not understood well. Two cortexin derivatives, short peptides EDR and DS with neuroprotective activity, were synthesized. According to the data of molecular modeling, these peptides are able to bind to the histone H1.3 protein. This can affect the conformation of histone H1.3, which leads to a change in the chromatin structure in the loci of some genes, in particular Fkbp1b encoding the FK506-binding protein. Electrophysiological processes associated with the Ca2+ exchange are disturbed in the pyramidal neurons of the hippocampus during aging of the brain. The Fkbp1b gene encodes peptidyl-prolyl cis-trans isomerase, regulating the release of calcium ions from the sarcoplasmic and endoplasmic reticulum of neurons. The activation of the Fkbp1b gene transcription under treatment with short peptides can promote the synthesis of its protein product and the activation of the Ca2+ release from organelles of the sarcoplasmic and endoplasmic reticulum of neurons, which, in turn, can lead to an increase in the functional activity of neurons.

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Authors and Affiliations

  1. Chita State Medical Academy, 672090, Chita, Russia

    B. I. Kuznik & S. O. Davydov

  2. Health Academy Innovation Clinic, 672000, Chita, Russia

    B. I. Kuznik & S. O. Davydov

  3. St. Petersburg Institute of Bioregulation and Gerontology, 197110, St. Petersburg, Russia

    E. S. Popravka, N. S. Lin’kova, L. S. Kozina & V. Kh. Khavinson

  4. Peter the Great St. Petersburg Polytechnic University, 195251, St. Petersburg, Russia

    N. S. Lin’kova

  5. Pavlov Institute of Physiology, Russian Academy of Sciences, 199034, St. Petersburg, Russia

    V. Kh. Khavinson

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  1. B. I. Kuznik
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  2. S. O. Davydov
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  3. E. S. Popravka
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  4. N. S. Lin’kova
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  5. L. S. Kozina
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  6. V. Kh. Khavinson
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Correspondence to N. S. Lin’kova.

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Translated by D. Novikova

Abbreviations: CNS, central nervous system; Brn3, brain-specific homeobox-containing transcription factor; CXCL12, chemokine of the CXC subfamily; EDR, pinealon; FK506, rapamycin; FKBP1b, FK506-binding protein 1b; IL-2, interleukin-2; mTORC1, mTOR1 complex; Pax6, aniridia type II protein or oculorhombin; PLB, propensity for ligand binding; Prox1, homeobox-containing protein 1 with Prospero domain; RyR, ryanodine receptor; sAHP, slow K+-dependent hyperpolarization.

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Kuznik, B.I., Davydov, S.O., Popravka, E.S. et al. Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b. Mol Biol 53, 299–307 (2019). https://doi.org/10.1134/S0026893319020092

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  • DOI: https://doi.org/10.1134/S0026893319020092

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