Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector86210.54101/ACEN.2022.2.7ReviewsОбзорыReview ArticleNMDA receptor antagonists as potential therapy in cerebellar degenerative disordersАнтагонисты NMDA-рецепторов как потенциальные средства для лечения нейродегенеративных заболеваний мозжечкаhttps://orcid.org/0000-0001-8384-5962BelozorOlga S.БелозорОльга Сергеевна
Russian Federation

assistant, Department of biological chemistry with courses in medical, pharmaceutical and toxicological chemistry

ассистент каф. биологической химии с курсами медицинской, фармацевтической и токсикологической химии

olsbelor@gmail.comhttps://orcid.org/0000-0002-3887-1413ShuvaevAndrey N.ШуваевАндрей Николаевич
Russian Federation

Associate Professor, Department of biomedical systems and complexes, Institute of Fundamental Biology and Biotechnology

доцент каф. медико-биологических систем и комплексов Института фундаментальной биологии и биотехнологии

olsbelor@gmail.comhttps://orcid.org/0000-0003-3299-1200FritslerYana V.ФрицлерЯна Викторовна
Russian Federation

postgraduate student, Department of biophysics, Institute of Fundamental Biology and Biotechnology

аспирант каф. биофизики Института фундаментальной биологии и биотехнологии

olsbelor@gmail.comhttps://orcid.org/0000-0003-0078-4733ShuvaevAnton N.ШуваевАнтон Николаевич
Russian Federation

Head, Research Institute of Molecular Medicine and Pathobiochemistry

рук. НИИ молекулярной медицины и патобиохимии

olsbelor@gmail.comKrasnoyarsk State Medical University named after Prof. V.F. Voino-YasenetskyФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого»Siberian Federal UniversityФГБОУ ВО «Сибирский федеральный университет3006202216258693006202230062022Copyright ©; 2022, Belozor O.S., Shuvaev A.N., Fritsler Y.V., Shuvaev A.N.Copyright ©; 2022, Белозор О.С., Шуваев А.Н., Фрицлер Я.В., Шуваев А.Н.2022Belozor O.S., Shuvaev A.N., Fritsler Y.V., Shuvaev A.N.Белозор О.С., Шуваев А.Н., Фрицлер Я.В., Шуваев А.Н.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/862

Cerebellar degeneration remains a poorly studied topic. Excitotoxicity, i.e. neuronal damage and death due to excess activation of postsynaptic N-methyl-D-aspartate receptors (NMDAR) by glutamate, is considered to be a universal mechanism of most neurodegenerative conditions. The use of antagonists that predominantly block NMDAR in cases of excitotoxicity is a very promising treatment strategy for neurodegenerative disorders.

This review presents the known structure and function of NMDAR. Information on studies investigating the use of NMDAR antagonists in the treatment of neurodegenerative diseases is provided. Creation of new therapies to correct excitotoxicity in various neurodegenerative disorders, for example, spinocerebellar ataxias, requires further study of the subunit composition and the role of NMDAR in the cerebellum. Treatment methods that combine the use of extrasynaptic NMDAR antagonists or synaptic NMDAR agonists with drugs that affect the total amount of glutamate in the synaptic cleft are promising.

Нейродегенерация мозжечка остаётся малоизученным вопросом. Универсальным механизмом развития большинства нейродегенеративных заболеваний считается эксайтотоксичность — повреждение и гибель нейронов в результате избыточной активации глутаматом постсинаптических N-метил-D-аспартат связывающих рецепторов (NMDAR). Одной из многообещающих стратегий лечения нейродегенеративных заболеваний является использование антагонистов, которые преимущественно блокируют NMDAR в эксайтотоксических сценариях.

В данном обзоре обсуждаются представления о строении и функциях NMDAR. Приведены сведения об исследованиях применения блокаторов NMDAR в лечении нейродегенеративных заболеваний. Для создания новых терапевтических стратегий коррекции эксайтотоксичности при различных нейродегенеративных заболеваниях, например, спиноцеребеллярных атаксиях, необходимы дальнейшие исследования субъединичного состава и роли NMDAR в мозжечке. Перспективны комплексные методы лечения, сочетающие применение блокаторов экстрасинаптических NMDAR или активаторов синаптических NMDAR с препаратами, влияющими на количество глутамата в синаптической щели.

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