sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.15372/SSMJ20190505sibmed-274Research ArticleОБЗОРЫREVIEWSH2S В НЕЙРОДЕГЕНЕРАЦИИ: «ДВУЛИКИЙ ЯНУС»H2S IN THE NEURODEGENERATION: A «DOUBLE-FACED JANUS»https://orcid.org/0000-0002-9236-6020КолесниковаЕ. Э.KolesnikovaE. E.

к.б.н.,

299011, г. Севастополь, просп. Нахимова, 2

candidate of biological sciences

299011, Sevastopol, Nakhimov av., 2

dr-kolesnikova@mail.ruИнститут морских биологических исследований им. А.О. Ковалевского РАНРоссияA.O. Kovalevsky Institute of Marine Biological Research of RASRussian Federation2019011120193954151Copyright © Колесникова Е.Э., 20192019Колесникова Е.Э.Kolesnikova E.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/274

В обзоре представлены данные литературы об участии сульфида водорода (сероводород, H<sub>2</sub>S) в качестве сигнальной молекулы в патогенезе нейродегенеративных заболеваний – болезни Паркинсона (БП), болезни Альцгеймера (БА), болезни Хантингтона (БХ) и бокового амиотрофического склероза (БАС). В центральной нервной системе уровень H<sub>2</sub>S определяется ферментами его синтеза – цистатионин-β-синтазой (CBS) и цистатионинγ-лиазой (CSE). H<sub>2</sub>S – газообразный трансмиттер, действие которого реализуется посредством химической и конформационной модификации молекул белков одновременно в объемных пулах клеток – «широком поле». Эффекты H<sub>2</sub>S отличаются разнонаправленностью, при достижении определенного порога сдвигаясь от нейропротекции к нейродегенерации. Оказалось, что процессы нейродегенерации опосредуются как повышенным (при БАС), так и пониженным (при БП, БА, БХ) уровнем продукции H<sub>2</sub>S, определяемым активностью отдельных ферментов его синтеза – CBS (БП, БА, БАС) и CSE (БХ), что приводит к развертыванию характерного для определенного заболевания паттерна неврологических событий. Патогенез нейродегенеративных заболеваний также предполагает изменения метаболизма серосодержащих аминокислот и тиол-дисульфидного гомеостаза как составной части H<sub>2</sub>S-зависимых сигнальных путей. Разнонаправленное негативное воздействие, вовлечение разных ферментов синтеза и продуктов преобразования сульфида водорода в механизмы развития патологии предполагает двойственную природу H<sub>2</sub>S в качестве сигнальной молекулы.

This paper reviews current literature data on the participation of hydrogen sulfide (H<sub>2</sub>S) in the pathogenesis of neurodegenerative disorders – Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). In the CNS the level of H<sub>2</sub>S is determined by the enzymes of its synthesis – cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H<sub>2</sub>S is a gasotransmitter, the action of which is realized through chemical and conformational modification of protein molecules simultaneously in spacious pools of cells – in a «broad field». The effects of H<sub>2</sub>S are highly divergent when a certain threshold is reached, it moves from the neuroprotection to the neurodegeneration. The neurodegeneration is mediated by both increased (in ALS) and decreased (PD, AD, HD) levels of H<sub>2</sub>S production, which is determined by the activity of different enzymes of its synthesis – CBS (PD, AD, ALS) or CSE (HD) – depending on the specificity of the certain disorder, that leads to the deployment of the especial pattern of neurological events. The disturbances in sulfur-containing amino acids metabolism and thiol-disulfide homeostasis are an integrative part in H<sub>2</sub>S-dependent mechanism of the neurodegeneration. The opposite/divergent negative effect of H<sub>2</sub>S, the involvement of different enzymes of its synthesis and some products of transformation in the pathological process suggest about the dual nature of H<sub>2</sub>S as a signaling molecule at neurodegenerative disorders.

сульфид водороданейродегенерацияболезнь Паркинсонаболезнь Альцгеймераболезнь Хантингтонабоковой амиотрофический склерозhydrogen sulfideneurodegenerationParkinson’s diseaseAlzheimer’s diseaseHuntington’s diseaseamyotrophic lateral sclerosisСредства федерального бюджета по НИОКТР № АААА-А18-118021490093-4 «Функциональные, метаболические и токсикологические аспекты существования гидробионтов и их популяций в биотопах с различным физико-химическим режимом» и № АААА-А18-118020790229-7 «Структурно- функциональная организация, продуктивность и устойчивость морских пелагических экосистем».This study was funded by the Federal Budget in the framework of the Research, Development, and Technological Work No. АААА-А18-118021490093-4 «Functional, metabolic, and toxicological aspects of the existence of aquatic organisms and their populations in biotopes with different physical and chemical regimes» and No. AAAA-A18-118020790229-7 «Structural and functional organization, productivity and sustainability of marine pelagic ecosystems».ReferencesИллариошкин С.Н. 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Mutant superoxide dismutase 1 forms aggregate in the brain mitochondria matrix of amyotrophic lateral sclerosis mice. J. Neurosci. 2005; 25 (10): 2463–2470. doi: 10.1523/JNEUROSCI.4385-04.2005.Vijayvergiya C., Beal M.F., Buck J., Manfredi G. Mutant superoxide dismutase 1 forms aggregate in the brain mitochondria matrix of amyotrophic lateral sclerosis mice. J. Neurosci. 2005; 25 (10): 2463–2470. doi: 10.1523/JNEUROSCI.4385-04.2005.Vural G., Gumusyayla S., Bektas H., Deniz O., Alisik M., Erel O. Impairment of dynamic thioldisulphide homeostasis in patients with idiopathic Parkinson’sdisease and its relationship with clinical stage of disease. Clin. Neurol. Neurosurg. 2017; 153: 50–55. doi: 10.1016/j.clineuro.2016.12.009.Vural G., Gumusyayla S., Bektas H., Deniz O., Alisik M., Erel O. Impairment of dynamic thioldisulphide homeostasis in patients with idiopathic Parkinson’sdisease and its relationship with clinical stage of disease. Clin. Neurol. 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The authors declare that there are no conflicts of interest present.