lvrachЛечащий ВрачLechaschi Vrach1560-51752687-118110.51793/OS.2024.27.5.013lvrach-1243Research ArticleАКТУАЛЬНАЯ ТЕМАTOPICAL THEMEЦистеиниловые лейкотриены как ключевые медиаторы иммунозависимых состояний и терапевтический потенциал антагониста лейкотриеновых рецепторов (монтелукаста). Часть 2Cysteine leukotrienes as key mediators of immune-dependent diseases and the therapeutic potential of the leukotriene receptor antagonist (montelukast). Part 2https://orcid.org/0000-0002-7691-4584АстафьеваН. Г.AstafievaN. G.

Астафьева Наталья Григорьевна, д.м.н., профессор, заведующая кафедрой клинической иммунологии и аллергологии

Россия, 410012, Саратов, ул. Б. Казачья, 112 

Natalia G. Astafieva, Dr. of Sci. (Med.), Professor, Head of the Department of Clinical Immunology and Allergology

112 Bolshaya Kazachya str., Saratov, 410012, Russia 

astang@mail.ruhttps://orcid.org/0000-0002-5955-1523МихайловаИ. Э.MikhailovaI. E.

Михайлова Ирина Эдуардовна, ассистент кафедры клинической иммунологии и аллергологии 

Россия, 410012, Саратов, ул. Б. Казачья, 112 

Irina Е. Mikhailova, Assistant of the Department of Clinical Immunology and Allergology

112 Bolshaya Kazachya str., Saratov, 410012, Russia 

irina7kis@mail.ruhttps://orcid.org/0009-0005-4171-117XГайсинаЕ. О.GaisinaE. O.

Гайсина Екатерина Олеговна, ассистент кафедры клинической иммунологии и аллергологии 

Россия, 410012, Саратов, ул. Б. Казачья, 112 

Ekaterina O. Gaisina, Assistant of the Department of Clinical Immunology and Allergology

112 Bolshaya Kazachya str., Saratov, 410012, Russia 

geo.15.03@mail.ruhttps://orcid.org/0000-0001-5737-7536ПерфиловаИ. А.PerfilovaI. A.

Перфилова Ирина Александровна, к.м.н., доцент кафедры клинической иммунологии и аллергологии 

Россия, 410012, Саратов, ул. Б. Казачья, 112 

Irina A. Perfilova, Cand. of Sci. (Med.), Associate Professor of the Department of Clinical Immunology and Allergology

112 Bolshaya Kazachya str., Saratov, 410012, Russia 

perfira@mail.ruhttps://orcid.org/0000-0001-8108-782XУдовиченкоЕ. Н.UdovichenkoE. N.

Удовиченко Екатерина Николаевна, к.м.н., доцент кафедры клинической иммунологии и аллергологии 

Россия, 410012, Саратов, ул. Б. Казачья, 112 

Ekaterina N. Udovichenko, Cand. of Sci. (Med.), Associate Professor of the Department of Clinical Immunology and Allergology

112 Bolshaya Kazachya str., Saratov, 410012, Russia 

udokate@mail.ruСаратовский государственный медицинский университет имени В. И. РазумовскогоРоссияFederal State Budgetary Educational Institution of Higher Education Saratov State Medical University named after V. I. Razumovsky of the Ministry of Health of the Russian FederationRussian Federation202407052024057787Copyright © Астафьева Н.Г., Михайлова И.Э., Гайсина Е.О., Перфилова И.А., Удовиченко Е.Н., 20242024Астафьева Н.Г., Михайлова И.Э., Гайсина Е.О., Перфилова И.А., Удовиченко Е.Н.Astafieva N.G., Mikhailova I.E., Gaisina E.O., Perfilova I.A., Udovichenko E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.lvrach.ru/jour/article/view/1243

Введение. Лейкотриены – липидные медиаторы, образующиеся при активации 5-липоксигеназного пути метаболизма арахидоната. Эти универсальные медиаторы широкого спектра действия влияют практически на все аспекты биологии млекопитающих. В клинической аллергологии и иммунологии они наиболее известны своей ролью в течении иммунозависимых заболеваний верхних и нижних дыхательных путей.Результаты. Краткая история их открытия и изучение роли антагонистов лейкотриеновых рецепторов (монтелукаста и его аналогов), выявление их терапевтического эффекта и возможных нежелательных явлений служат важной иллюстрацией для понимания включения монтелукаста в национальные, международные клинические рекомендации и консенсусы. Монтелукаст – антагонист цистеинил-лейкотриеновых рецепторов 1, ингибирует эффекты лейкотриенов и широко используется для лечения астмы и аллергического ринита, включен в клинические рекомендации по лечению указанных заболеваний. Препарат вмешивается в молекулярные сигнальные пути, продуцируемые лейкотриенами в различных клетках и тканях человеческого организма. В последние годы наблюдается новая терапевтическая стратегия – репозиционирование существующих препаратов. Противовоспалительное действие монтелукаста не ограничивается респираторной системой, а имеет более системный характер, что привело к развитию клинических исследований, направленных на повторное использование монтелукаста для лечения различных воспалительных состояний, в частности, ряда нейродегенеративных заболеваний. Недавние достижения в исследованиях нейровоспаления привели к открытию нескольких новых воспалительных путей, регулирующих многие церебральные патологии. С помощью фармакологических и генетических исследований было показано, что рецепторы цистеиниловых лейкотриенов участвуют в патогенезе болезни Альцгеймера и других нейродегенеративных/неврологических заболеваний, таких как болезнь Паркинсона, рассеянный склероз и эпилепсия. В данном обновленном обзоре также освещаются исследования терапевтического потенциала монтелукаста, выходящие за рамки клинических рекомендаций по лечению ринита и астмы.

Background. Cysteine leukotrienes are lipid mediators formed upon activation of the 5-lipoxygenase pathway of arachidonate metabolism. These are universal mediators with a wide spectrum of action, affecting almost all aspects of mammalian biology. In clinical allergy and immunology they are best known for their role in the formation of immune-related diseases of the upper and lower respiratory tract.Results. A brief history of their discovery and study of the role of leukotriene receptor antagonists (montelukast and its analogs), identification of their therapeutic effect and possible undesirable effects are an important illustration for understanding the inclusion of montelukast in national, international clinical guidelines and consensuses. Montelukast is a cysteinyl-leukotriene receptor 1 antagonist, inhibits the effects of leukotrienes and is widely used for the treatment of asthma and allergic rhinitis; it is included in the clinical guidelines for the treatment of these diseases. The drug interferes with molecular signalling pathways produced by leukotrienes in various cells and tissues of the human body. In recent years, a new therapeutic strategy has been observed – repositioning of existing drugs. The anti-inflammatory effects of montelukast are not limited to the respiratory system, but are more systemic in nature, which has led to the development of clinical studies aimed at the reuse of montelukast for the treatment of various inflammatory conditions, particularly for the treatment of several neurodegenerative diseases. Recent advances in neuroinflammation research have led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies. Through pharmacological and genetic studies, cysteinyl leukotriene receptors have been shown to be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative/neurological diseases such as Parkinson's disease, multiple sclerosis and epilepsy. This updated review will also highlight research into the therapeutic potential of montelukast beyond clinical guidelines for rhinitis and asthma.

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