r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2021-26-5-4-15r-n-j-222Research ArticleОБЗОРLITERATURE REVIEWИммунопатогенез и подходы к разработке иммунотерапии нейродегенеративных и цереброваскулярных заболеваний с когнитивными нарушениями. Современное состояние проблемы и перспективыImmunopathogenesis and immunotherapeutic approaches of neurodegenerative and cerebrovascular diseases with cognitive impairment. The current state of the problem and prospectshttps://orcid.org/0000-0002-6914-258XСмирноваА. А.SmirnovaA. A.

197376, Санкт-Петербург

197376, Saint Petersburg

https://orcid.org/0000-0002-4776-2999ПраховаЛ. Н.PrakhovaL. N.

Прахова Лидия Николаевна

197376, Санкт-Петербург

197376, Saint Petersburg

l.n.prakhova@hotmail.comhttps://orcid.org/0000-0002-9822-5982ИльвесA. Г.IlvesA. G.

197376, Санкт-Петербург

197376, Saint Petersburg

ФГБУН Институт мозга человека им. Н.П. Бехтеревой Российской академии наукРоссияN.P. Bechtereva Institute of the Human Brain of the Russian Academy of SciencesRussian Federation202111112021265415Copyright © Смирнова А.А., Прахова Л.Н., Ильвес A.Г., 20212021Смирнова А.А., Прахова Л.Н., Ильвес A.Г.Smirnova A.A., Prakhova L.N., Ilves A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/222

Когнитивные нарушения (КН) представляют серьезную проблему современного общества. Наиболее частыми причинами развития КН являются нейродегенеративные заболевания (прежде всего, болезнь Альцгеймера (БА) и цереброваскулярные расстройства). В настоящее время стратегия терапии этих заболеваний имеет ограниченную эффективность в отношении восстановления когнитивных функций и течения болезни, хотя и способна замедлять темпы когнитивного снижения.

Понимание иммунопатогенеза нейродегенеративных и цереброваскулярных заболеваний определяет новые мишени и подходы к лечению. Подавление нейровоспаления целесообразно уже на ранних стадиях когнитивного снижения, когда информативность рутинного клинического, лабораторного и инструментального обследования пациентов недостаточна для уточнения причин КН.

Статья суммирует современные представления об иммунопатогенезе БА и хронической церебральной ишемии (ХЦИ). Механизм развития нейровоспаления представлен как каскад последовательных событий, замыкающихся в конечном итоге в самоподдерживающийся воспалительный ответ. В качестве потенциальных точек приложения иммуномодулирующей терапии рассмотрены молекулярные фрагменты, ассоциированные с повреждением, и воспринимающие их специфические рецепторы (паттерн-распознающие рецепторы), внутриклеточная передача сигнала в микроглиальных клетках, цитокины и адгезионные молекулы. Приведены сведения о современном уровне разработанности иммунотерапии БА и ХЦИ и дальнейшие перспективы ее применения.

Cognitive impairments (CI) are a serious problem in modern society, because they significantly reduce patients’ quality of life and tend to progress. Age-related diseases such as neurodegenerative — first of all Alzheimer’s disease (AD) and cerebrovascular disorders are key causes leading to CI. At present, approaches to treating these diseases have limited effectiveness in restoring cognitive functions, and do not change disease course, although they can slow cognitive decline.

Understanding the immunopathogenesis of neurodegenerative and cerebrovascular diseases defines new targets and approaches to their treatment. In addition, suppression of neuroinflammation is advisable in the cases of early nonclarified cognitive decline, when information from routine medical, laboratory and instrumental examination of patients is insufficient to identify the causes of CI.

This article summarizes current understanding of the immunopathogenesis of AD and chronic cerebral ischemia. The mechanism of neuroinflammation is presented as a cascade of sequential events that are closed in a self-perpetuating inflammatory response in the end. So called damage-associated molecular patterns, specific receptors that can bind them (pattern recognition receptors), intracellular signal transduction in microglia, cytokines and adhesion molecules are considered as potential points of application of immunomodulatory therapy. The review provides information on the current level of development of immunotherapy of AD, chronic cerebral ischemia and offers the prospect of its application.

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