Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute56279110.23868/gc562791ReviewsНаучные обзорыReview ArticleContribution of 25-hydroxycholesterol to the cross-interaction of the immune and nervous systemsВклад 25-гидроксихолестерина в перекрёстное взаимодействие иммунной и нервной системhttps://orcid.org/0000-0003-2949-00269856-1498ZakyrjanovaGuzalia F.ЗакирьяноваГузалия Фаритовна
Russian Federation

Cand. Sci. (Biol.)

к.б.н.

farraguz12@gmail.comhttps://orcid.org/0000-0002-4611-75092071-9047TsentsevitskyAndrei N.ЦенцевицкийАндрей Николаевич
Russian Federation

Cand. Sci. (Biol.)

к.б.н.

atsen@list.ruhttps://orcid.org/0000-0003-4789-18007614-5148GiniatullinArthur R.ГиниатуллинАртур Рауфович
Russian Federation

Cand. Sci. (Biol.)

к.б.н.

kvestor80@rambler.ruhttps://orcid.org/0000-0001-8092-9431NghomsiSonia Madeleine FogaingНгомсиСоня Маделен Фоген
Russian Federation
danicastats@gmail.comhttps://orcid.org/0000-0002-5581-7793KuznetsovaEva A.КузнецоваЕва Андреевна
Russian Federation
eva.korshak@mail.ruhttps://orcid.org/0000-0002-1432-34557543-0918PetrovAlexey M.ПетровАлексей Михайлович
Russian Federation

Dr. Sci. (Biol.)

д.б.н.

apneurosci@gmail.comKazan Institute of Biochemistry and Biophysics, Federal Research Center “Kazan Scientific Center of RAS”, Russian Academy of SciencesКазанский институт биохимии и биофизики — обособленное структурное подразделение Федерального исследовательского центра «Казанский научный центр Российской академии наук»Kazan State Medial UniversityКазанский государственный медицинский университетКazan Federal UniversityКазанский федеральный университет01112023151220231842692802107202319082023Copyright ©; 2023, Eco-VectorCopyright ©; 2023, Эко-Вектор2023Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://genescells.ru/2313-1829/article/view/562791

25-hydroxycholesterol (25HC) is produced from cholesterol by cholesterol-25-hydroxylase, and its expression, similar to the 25HC level, increases significantly in macrophages, dendritic cells, and microglia during an inflammatory reaction. In turn, 25HC acts on many immune cells; therefore, it can modulate the course of the inflammatory reaction and prevent the penetration of viruses into cells. Data are accumulating about the involvement of 25HC in the regulation of synaptic transmission in both the central and peripheral nervous systems. 25HC production is increased not only during inflammation but in certain neurodegenerative diseases, such as Alzheimer’s disease and amyotrophic lateral sclerosis; thus, this hydroxycholesterol can be important in the adaptation of synaptic activity to inflammatory conditions, pathogenesis of neurodegenerative diseases, and formation of synaptic dysfunctions. The targets of 25HC in the nervous system are glutamate NMDA receptors, liver X-receptors, and estrogen receptors. 25HC can also directly influence the properties of synaptic membranes by changing the formation of membrane microdomains (lipid rafts) where proteins, which are important for synaptic plasticity, are clustered. Current data indicate that the effects of 25HC strongly depend on its concentration and “context” (norm, pathology, and presence of an inflammatory reaction) in which the effect of 25HC is being investigated. This minireview focused on the key aspects of the action of 25HC as both a local regulator of cholesterol homeostasis and a paracrine molecule that realizes the influence of inflammation on neurotransmission processes in the central and peripheral nervous systems.

25-гидроксихолестерин (25ГХ) образуется из холестерина при участии фермента холестерин-25-гидроксилазы, экспрессия которой, как и уровень 25ГХ, значительно увеличивается в макрофагах, дендритных клетках и микроглии при воспалительной реакции. В свою очередь 25ГХ действует на многие иммунные клетки, модулируя течение воспалительной реакции и препятствуя проникновению вирусов в клетки. Накапливаются данные об участии 25ГХ в регуляции синаптической передачи как в центральной, так и периферической нервной системах. Учитывая повышенную продукцию 25ГХ не только при воспалении, но при ряде нейродегенеративных заболеваний (болезни Альцгеймера и боковом амиотрофическом склерозе), этот гидроксихолестерин может иметь значение в адаптации синаптической активности к воспалительным условиям, а также участвовать в патогенезе нейродегенеративных заболеваний и формировании синаптических дисфункций. Мишенями 25ГХ в нервной системе являются глутаматные NMDA-рецепторы, печёночные Х-рецепторы и эстрогеновые рецепторы. К тому же 25ГХ может напрямую влиять на свойства синаптических мембран, изменяя формирование мембранных микродоменов (липидных рафтов) — компартментов, где сосредоточены белки, важные в синаптической пластичности. Текущие данные указывают на то, что эффекты 25ГХ сильно зависят от концентрации и «контекста» (норма, патология, наличие воспалительной реакции), в котором исследуется его действие.

В данном мини-обзоре мы сфокусировались на ключевых аспектах действия 25ГХ как локального регулятора гомеостаза холестерина и как паракринной молекулы, реализующей влияние воспаления на процессы нейропередачи в центральной и периферической нервной системе.

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