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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Genes &amp; Cells</journal-id><journal-title-group><journal-title xml:lang="en">Genes &amp; Cells</journal-title><trans-title-group xml:lang="ru"><trans-title>Гены и Клетки</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Genes and Cells</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-1829</issn><issn publication-format="electronic">2500-2562</issn><publisher><publisher-name xml:lang="en">Human Stem Cells Institute</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">546022</article-id><article-id pub-id-type="doi">10.23868/gc546022</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Reviews</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Научные обзоры</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Glymphatic dysfunction in the pathogenesis of neurodegenerative diseases and pathological aging</article-title><trans-title-group xml:lang="ru"><trans-title>Глимфатическая дисфункция в патогенезе нейродегенеративных заболеваний и патологического старения</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7670-6566</contrib-id><contrib-id contrib-id-type="spin">3939-3590</contrib-id><name-alternatives><name xml:lang="en"><surname>Shirolapov</surname><given-names>Igor V.</given-names></name><name xml:lang="ru"><surname>Широлапов</surname><given-names>Игорь Викторович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>ishirolapov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1709-6195</contrib-id><contrib-id contrib-id-type="spin">9348-2044</contrib-id><name-alternatives><name xml:lang="en"><surname>Zakharov</surname><given-names>Alexander V.</given-names></name><name xml:lang="ru"><surname>Захаров</surname><given-names>Александр Владимирович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>a.v.zaharov@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0027-1786</contrib-id><contrib-id contrib-id-type="spin">9908-6292</contrib-id><name-alternatives><name xml:lang="en"><surname>Bulgakova</surname><given-names>Svetlana V.</given-names></name><name xml:lang="ru"><surname>Булгакова</surname><given-names>Светлана Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>д.м.н., доцент</p></bio><email>s.v.bulgakova@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1878-7951</contrib-id><contrib-id contrib-id-type="spin">6820-6072</contrib-id><name-alternatives><name xml:lang="en"><surname>Khivintseva</surname><given-names>Elena V.</given-names></name><name xml:lang="ru"><surname>Хивинцева</surname><given-names>Елена Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>e.v.hivinceva@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0926-8551</contrib-id><contrib-id contrib-id-type="spin">3075-1082</contrib-id><name-alternatives><name xml:lang="en"><surname>Sergeeva</surname><given-names>Mariya S.</given-names></name><name xml:lang="ru"><surname>Сергеева</surname><given-names>Мария Станиславовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Biol.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.б.н., доцент</p></bio><email>m.s.sergeeva@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3522-6803</contrib-id><contrib-id contrib-id-type="spin">2469-9414</contrib-id><name-alternatives><name xml:lang="en"><surname>Romanchuk</surname><given-names>Natalia P.</given-names></name><name xml:lang="ru"><surname>Романчук</surname><given-names>Наталья Петровна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Cand. Sci. (Med.), Associate Professor</p></bio><bio xml:lang="ru"><p>к.м.н., доцент</p></bio><email>n.p.romanchuk@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8055-1958</contrib-id><contrib-id contrib-id-type="spin">6326-6884</contrib-id><name-alternatives><name xml:lang="en"><surname>Pavlova</surname><given-names>Olga N.</given-names></name><name xml:lang="ru"><surname>Павлова</surname><given-names>Ольга Николаевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Biol.), Associate Professor</p></bio><bio xml:lang="ru"><p>д.б.н., доцент</p></bio><email>o.n.pavlova@samsmu.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2881-6648</contrib-id><contrib-id contrib-id-type="spin">2149-5148</contrib-id><name-alternatives><name xml:lang="en"><surname>Kazantsev</surname><given-names>Victor B.</given-names></name><name xml:lang="ru"><surname>Казанцев</surname><given-names>Виктор Борисович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Phys.-Math.), Professor</p></bio><bio xml:lang="ru"><p>д.ф.-м.н., профессор</p></bio><email>v.b.kazantsev@samsmu.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Samara State Medical University</institution></aff><aff><institution xml:lang="ru">Самарский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">National Research Lobachevsky State University of Nizhny Novgorod</institution></aff><aff><institution xml:lang="ru">Национальный исследовательский Нижегородский государственный университет им. Н.И. Лобачевского</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2023-11-11" publication-format="electronic"><day>11</day><month>11</month><year>2023</year></pub-date><pub-date date-type="pub" iso-8601-date="2023-12-15" publication-format="electronic"><day>15</day><month>12</month><year>2023</year></pub-date><volume>18</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>309</fpage><lpage>322</lpage><history><date date-type="received" iso-8601-date="2023-07-12"><day>12</day><month>07</month><year>2023</year></date><date date-type="accepted" iso-8601-date="2023-10-17"><day>17</day><month>10</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2023, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2023, Эко-Вектор</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2027-02-20"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref></license></permissions><self-uri xlink:href="https://genescells.ru/2313-1829/article/view/546022">https://genescells.ru/2313-1829/article/view/546022</self-uri><abstract xml:lang="en"><p>Recently, the concept of the glymphatic system as a highly organized perivascular network has been formed, which by hydrodynamic approach, with the key participation of aquaporin-4 as a central molecule, connects the cerebrospinal fluid with the lymphatic vessels of the meninges through the brain interstitium. The latest scientific works demonstrates the potential role of glymphatic dysfunction in the development of neurodegeneration and pathological aging. Although the precise molecular mechanisms of glymphatic pathway function have not yet been fully characterized, the critical processes underlying cerebral solute transport and clearance of amyloid and metabolites have been largely elucidated. The complex interaction between a number of age-associated factors, including cellular aging, disturbances in the sleep-wake cycle with changes in sleep architecture and quality, low-grade systemic inflammation, and the development of concomitant diseases, determines not only life expectancy in general, but also forms the basis of healthy and unhealthy aging the brain in particular. Imbalances in homeostatic functions, changes in the activity of glymphatic clearance and the blood-brain barrier that support the exchange of fluid and solutes in cerebral tissue, which can be observed both normally with physiological aging and with the development of neuropathology, have longitudinal consequences ranging from disruption of synaptic signal transmission to onset of neurodegenerative processes.</p> <p>This review analyzes the current scientific information in this area of research, details the features of the perivascular glial-mediated transport system, and discusses how its dysfunction plays a fundamental role in the pathological accumulation of metabolites during aging, the development of age-associated changes in the brain, and the progression of neurodegenerative diseases.</p></abstract><trans-abstract xml:lang="ru"><p>Недавно сформирована концепция глимфатической системы как высокоорганизованной периваскулярной сети, которая гидродинамическим путём с ключевым участием аквапорина-4 в качестве центральной молекулы соединяет спинномозговую жидкость с лимфатическими сосудами мозговых оболочек через интерстиций головного мозга. Современные исследования демонстрируют потенциальную роль глимфатической дисфункции в развитии процессов нейродегенерации и патологического старения. Несмотря на то, что точные молекулярные механизмы функционирования глимфатического пути ещё полностью не охарактеризованы, решающие процессы, лежащие в основе церебрального транспорта растворённых веществ и клиренса амилоида и метаболитов, уже во многом определены. Сложное взаимодействие между рядом возраст-ассоциированных факторов, включая клеточное старение, нарушение в цикле сон–бодрствование с изменением архитектуры и качества сна, вялотекущее системное воспаление, развитие сопутствующих заболеваний, не только определяет продолжительность жизни в целом, но и формирует основы здорового и нездорового старения мозга в частности. Дисбаланс гомеостатических функций, изменения в активности глимфатического клиренса и гематоэнцефалического барьера, поддерживающих обмен жидкости и растворённых веществ в церебральной ткани, которые могут наблюдаться как в норме при физиологическом старении, так и при развитии нейропатологии, имеют лонгитюдные последствия — от нарушения синаптической передачи сигнала до начала нейродегенеративных процессов.</p> <p>В настоящем обзоре проанализирована актуальная научная информация в данной области исследований, детально описаны особенности периваскулярной глиально-опосредованной системы транспорта и обсуждается фундаментальная роль её дисфункции в патологическом накоплении метаболитов при старении, развитии возраст-ассоциированных изменений в мозге и прогрессировании нейродегенеративных заболеваний.</p></trans-abstract><kwd-group xml:lang="en"><kwd>glymphatic pathway, aquaporin-4, dysfunction, clearance, neurodegeneration, amyloid, blood-brain barrier</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>глимфатический путь</kwd><kwd>аквапорин 4-го типа</kwd><kwd>дисфункция</kwd><kwd>клиренс</kwd><kwd>нейродегенерация</kwd><kwd>амилоид</kwd><kwd>гематоэнцефалический барьер</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Bah TM, Siler DA, Ibrahim AH, et al. 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