epilepsiaEpilepsy and paroxysmal conditionsЭпилепсия и пароксизмальные состояния2077-83332311-4088IRBIS LLC10.17749/2077-8333/epi.par.con.2025.239epilepsia-1214Research ArticleSCIENTIFIC SURVEYSНАУЧНЫЕ ОБЗОРЫThe role of microRNAs as regulators of systemic inflammatory response in anticonvulsant-induced metabolic syndromeРоль микроРНК как регуляторов системного воспалительного ответа при метаболическом синдроме, индуцированном противоэпилептическими препаратамиhttps://orcid.org/0000-0002-2840-837XШнайдерН. А.ShnayderN. A.

Шнайдер Наталья Алексеевна, д.м.н., проф.

WoS ResearcherID: M-7084-2014. Scopus Author ID: 24503222300

ул. Бехтерева, д. 3, Санкт-Петербург 192019;

ул. Партизана Железняка, д. 1, Красноярск 660022

Natalia A. Shnayder, Dr. Sci. Med., Prof.

WoS ResearcherID: M-7084-2014. Scopus Author ID: 24503222300

3 Bekhterev Str., Saint Petersburg 192019;

1 Partizan Zheleznyak Str., Krasnoyarsk 660022

naschnaider@yandex.ruhttps://orcid.org/0009-0005-5895-1778ПекарецН. А.PekaretsN. A.

Пекарец Николай Александрович

ул. Бехтерева, д. 3, Санкт-Петербург 192019

Nikolai A. Pekarets

3 Bekhterev Str., Saint Petersburg 192019

https://orcid.org/0009-0002-5934-3449ПекарецН. И.PekaretsN. I.

Пекарец Наталья Игоревна

ул. Красного Восстания, д. 1, Иркутск 664003

Natalia I. Pekarets

1 Krasnogo Vosstaniya Str., Irkutsk 664003

https://orcid.org/0000-0002-7836-5179БыковЮ. Н.BykovYu. N.

Быков Юрий Николаевич, д.м.н., проф.

WoS ResearcherID: S-6938-2016. Scopus Author ID: 57200671414

ул. Красного Восстания, д. 1, Иркутск 664003

Yury N. Bykov, Dr. Sci. Med., Prof.

WoS ResearcherID: S-6938-2016. Scopus Author ID: 57200671414

1 Krasnogo Vosstaniya Str., Irkutsk 664003

https://orcid.org/0000-0001-8279-4198ГречкинаВ. В.GrechkinaV. V.

Гречкина Виолетта Владимировна

Scopus Author ID: 58076147700

ул. Бехтерева, д. 3, Санкт-Петербург 192019

Violetta V. Grechkina

Scopus Author ID: 58076147700

3 Bekhterev Str., Saint Petersburg 192019

https://orcid.org/0000-0003-4639-6365ДмитренкоД. В.DmitrenkoD. V.

Дмитренко Диана Викторовна, д.м.н.

WoS ResearcherID: H-7787-2016

ул. Партизана Железняка, д. 1, Красноярск 660022

Diana V. Dmitrenko, Dr. Sci. Med.

1 Partizan Zheleznyak Str., Krasnoyarsk 660022

WoS ResearcherID: H-7787-2016

https://orcid.org/0000-0002-8493-0058ПетроваМ. М.PetrovaM. M.

Петрова Марина Михайловна, д.м.н., проф.

WoS ResearcherID: L-5623-2014. Scopus Author ID: 23987271200

ул. Партизана Железняка, д. 1, Красноярск 660022

Marina M. Petrova, Dr. Sci. Med., Prof.

1 Partizan Zheleznyak Str., Krasnoyarsk 660022

WoS ResearcherID: L-5623-2014. Scopus Author ID: 23987271200

https://orcid.org/0000-0003-1874-9434НасыроваР. Ф.NasyrovaR. F.

Насырова Регина Фаритовна, д.м.н.

WoS ResearcherID: H-7787-2016

ул. Бехтерева, д. 3, Санкт-Петербург 192019;

пр-т Ленина, д. 92, Тула 300012

Regina F. Nasyrova, Dr. Sci. Med.

WoS ResearcherID: H-7787-2016

3 Bekhterev Str., Saint Petersburg 192019;

92 Lenin Ave., Tula 300012

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Centre for Psychiatry and Neurology; Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Centre for Psychiatry and NeurologyRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Иркутский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияIrkutsk State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииРоссияVoino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение высшего образования «Тульский государственный университет»РоссияBekhterev National Medical Research Centre for Psychiatry and Neurology; Tula State UniversityRussian Federation202518072025172208226Copyright © Shnayder N.A., Pekarets N.A., Pekarets N.I., Bykov Y.N., Grechkina V.V., Dmitrenko D.V., Petrova M.M., Nasyrova R.F., 20252025Шнайдер Н.А., Пекарец Н.А., Пекарец Н.И., Быков Ю.Н., Гречкина В.В., Дмитренко Д.В., Петрова М.М., Насырова Р.Ф.Shnayder N.A., Pekarets N.A., Pekarets N.I., Bykov Y.N., Grechkina V.V., Dmitrenko D.V., Petrova M.M., Nasyrova R.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epilepsia.su/jour/article/view/1214

Background. Metabolic syndrome induced by antiepileptic drugs (AED-MetS) is a serious adverse reaction (AR) that reduces the quality of life of patients with epilepsy and increases the risk of comorbid cardiovascular disorders affecting life expectancy. The risk of developing AED-MetS varies depending on various factors that account for a search for sensitive and specific biomarkers to predict its development, prevention, diagnosis and correction as well as related main domains (hypertension, dyslipidemia, central obesity, type 2 diabetes mellitus). Systemic inflammatory response and oxidative stress are important arms in both epileptogenesis and neurodegeneration, as well as AED-MetS pathogenesis.Objective: Systematization of the results from preclinical and clinical studies on the role of circulating blood microRNAs in the development and adverse course of the systemic inflammatory response as one of AED-MetS main domains in patients with epilepsy.Material and methods. The analysis of the results of fundamental and clinical studies on circulating microRNAs as epigenetic biomarkers of systemic inflammatory reactions in the mechanism of MetS and AED-MetS pathogenesis, which were included in the databases Google Scholar, PubMed/MEDLINE, MDPI, Scopus, and eLibrary, was carried out over the last decade (2014– 2024).Results. A systematic review has demonstrated that microRNAs can act as promising epigenetic biomarkers of AED-MetS, however, the role for different microRNAs and their paralogs on the development of this AR varies. As part of the current study, a microRNA signature was proposed depending on the risk and severity of the systemic inflammatory response and associated oxidative stress (the leading mechanisms of AED-MetS pathogenesis). The proposed signature consists of three groups of microRNAs, depending on their role in regulating the systemic inflammatory response: low, medium, and high risk.Conclusion. The role of microRNAs in regulating the systemic inflammatory response in AED-MetS requires to be further investigated and results of basic research translated into real-world clinical practice, since the studied microRNAs can not only trigger and exacerbate AED-MetS, but also initiate or support the neurodegenerative processes underlying epileptogenesis.

Актуальность. Метаболический синдром, индуцированный приемом противоэпилептических препаратов (ПЭП-МетС) является серьезной нежелательной реакцией (НР), которая снижает качество жизни больных эпилепсией и повышает риск коморбидных сердечно-сосудистых заболеваний, влияющих на продолжительность жизни. Риск возникновения данной НР варьируется в зависимости от различных факторов, которые определяют поиск чувствительных и специфичных биомаркеров для прогнозирования развития, профилактики, диагностики и коррекции ПЭП-МетС и его основных доменов (артериальная гипертензия, дислипидемия, центральное ожирение, сахарный диабет 2-го типа). Системный воспалительный ответ и оксидативный стресс – важные звенья как эпилептогенеза и нейродегенерации, так и патогенеза ПЭП-МетС.Цель: систематизация результатов доклинических и клинических исследований роли микроРНК в развитии и неблагоприятном течении системного воспаления и оксидативного стресса, в эпилептогенезе и патогенезе ПЭП-МетС у пациентов с эпилепсией.Материал и методы. Проведен анализ результатов фундаментальных и клинических исследований циркулирующих микроРНК как эпигенетических биомаркеров системных воспалительных реакций в механизме патогенеза МетС и ПЭП-МетС, поступивших в базы данных Google Scholar, PubMed/MEDLINE, MDPI, Scopus, и eLibrary за последнее десятилетие (2014–2024 гг.).Результаты. Систематический обзор продемонстрировал, что микроРНК могут выступать как перспективные эпигенетические биомаркеры ПЭП-МетС, однако роль различных микроРНК и их паралогов в развитии данной НР вариабельна. В рамках настоящего исследования предложена сигнатура микроРНК в зависимости от риска развития и тяжести течения системного воспалительного ответа и ассоциированного с ним оксидативного стресса (ведущих механизмов патогенеза ПЭП-МетС). Данная сигнатура включает три группы микроРНК в зависимости от их роли в регуляции системного воспалительного ответа: низкий, средний, высокий риск.Заключение. Роль микроРНК в регуляции системного воспалительного ответа при ПЭП-МетС нуждается в дальнейшем изучении и трансляции результатов фундаментальных исследований в реальную клиническую практику, поскольку рассмотренные микроРНК могут не только запускать и усугублять ПЭП-МетС, но и инициировать или поддерживать нейродегенеративные процессы, лежащие в основе эпилептогенеза.

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The authors declare that there are no conflicts of interest present.