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Prospects for Gene Therapy of Epilepsy Using Calcium-Acivated Potassium Channel Vectors

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Abstract

Epilepsy is one of the widespread neurological human diseases, and nearly a third of patients are not completely relieved from epileptic seizures by anticonvulsants. Therefore, the search and development of new treatment approaches for epilepsy remains one of the urgent challenges for modern basic neurobiology and clinical neurology. In recent years, gene therapy for epilepsy has been attracting ever-increasing attention of researchers. Currently, the priority trend of gene therapy is the overexpression of the genes in neurons, which reduce the activity of neural networks in the epileptic focus, including the expression of both channel proteins and inhibitory neuromodulators. In this review, we address the possibility of using overexpression of calcium-activated potassium channels. In this review, we address the possibility of using overexpression of calcium-activated potassium channels. The advantage of choosing this subgroup of channels for gene therapy lies in the fact that maximal activation of calcium-activated potassium channels and their hyperpolarizing effects are implemented during intracellular calcium accumulation, which is exactly observed during epileptic activity in neural networks. Several subtypes of calcium-activated potassium channels are expressed in mammalian cells. Analysis of the available experimental and clinical data shows that intermediate-conductance and small-conductance calcium-activated potassium channels (IK and SK channels, respectively) may have a high potential for gene therapy for epilepsy.

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Funding

The writing of the review was supported by the Ministry of Science and Higher Education of the Russian Federation, agreement no. 075-15-2020-801.

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Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

    E. S. Nikitin & P. M. Balaban

  2. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    A. V. Zaitsev

  3. Almazov National Medical Research Center, St. Petersburg, Russia

    A. V. Zaitsev

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  1. E. S. Nikitin
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  2. P. M. Balaban
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  3. A. V. Zaitsev
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Conceptualization (E.S.N., A.V.Z.); rough draft preparation (E.S.N., A.V.Z.); editing and preparing the final version (E.S.N., P.M.B., A.V.Z.).

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Correspondence to E. S. Nikitin.

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The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 7, pp. 795–806https://doi.org/10.31857/S0869813922070068.

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Nikitin, E.S., Balaban, P.M. & Zaitsev, A.V. Prospects for Gene Therapy of Epilepsy Using Calcium-Acivated Potassium Channel Vectors. J Evol Biochem Phys 58, 1065–1074 (2022). https://doi.org/10.1134/S0022093022040111

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