<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<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">Russian Journal of Physiotherapy, Balneology and Rehabilitation</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Physiotherapy, Balneology and Rehabilitation</journal-title><trans-title-group xml:lang="ru"><trans-title>Физиотерапия, бальнеология и реабилитация</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1681-3456</issn><issn publication-format="electronic">2413-2969</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">677844</article-id><article-id pub-id-type="doi">10.17816/rjpbr677844</article-id><article-id pub-id-type="edn">AGYEDK</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Review</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>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">Physical Activity and the Myokine Irisin in Non-pharmacological Treatment of Alzheimer Disease</article-title><trans-title-group xml:lang="ru"><trans-title>Физическая активность и миокин иризин как немедикаментозный подход к лечению болезни Альцгеймера</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>体育锻炼与肌源因子鸢尾素： 阿尔茨海默病非药物治疗的新路径</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-2126-1813</contrib-id><name-alternatives><name xml:lang="en"><surname>Gibizov</surname><given-names>Yuriy A.</given-names></name><name xml:lang="ru"><surname>Гибизов</surname><given-names>Юрий Аланович</given-names></name><name xml:lang="zh"><surname>Gibizov</surname><given-names>Yuriy A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>sadreit@rambler.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-5148-6794</contrib-id><name-alternatives><name xml:lang="en"><surname>Vagapova</surname><given-names>Liza B.</given-names></name><name xml:lang="ru"><surname>Вагапова</surname><given-names>Лиза Беслановна</given-names></name><name xml:lang="zh"><surname>Vagapova</surname><given-names>Liza B.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>vagapova.li@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-5879-7570</contrib-id><name-alternatives><name xml:lang="en"><surname>Aguzarova</surname><given-names>Alina O.</given-names></name><name xml:lang="ru"><surname>Агузарова</surname><given-names>Алина Олеговна</given-names></name><name xml:lang="zh"><surname>Aguzarova</surname><given-names>Alina O.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>aguzarova20021410@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-2589-3538</contrib-id><name-alternatives><name xml:lang="en"><surname>Nazarova</surname><given-names>Julia V.</given-names></name><name xml:lang="ru"><surname>Назарова</surname><given-names>Юлия Валерьевна</given-names></name><name xml:lang="zh"><surname>Nazarova</surname><given-names>Julia V.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>nazar-yulia2015@yandex.ru</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-5204-4386</contrib-id><name-alternatives><name xml:lang="en"><surname>Zotkina</surname><given-names>Yana A.</given-names></name><name xml:lang="ru"><surname>Зоткина</surname><given-names>Яна Андреевна</given-names></name><name xml:lang="zh"><surname>Zotkina</surname><given-names>Yana A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>zotckina.yana@yandex.ru</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0006-2719-664X</contrib-id><name-alternatives><name xml:lang="en"><surname>Atamanyuk</surname><given-names>Ekaterina A.</given-names></name><name xml:lang="ru"><surname>Атаманюк</surname><given-names>Екатерина Алексеевна</given-names></name><name xml:lang="zh"><surname>Atamanyuk</surname><given-names>Ekaterina A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>ekaterina_ataman@mail.ru</email><xref ref-type="aff" rid="aff5"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-9183-6888</contrib-id><name-alternatives><name xml:lang="en"><surname>Rodikova</surname><given-names>Mariia M.</given-names></name><name xml:lang="ru"><surname>Родикова</surname><given-names>Мария Максимовна</given-names></name><name xml:lang="zh"><surname>Rodikova</surname><given-names>Mariia M.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>rodikova_00@mail.ru</email><xref ref-type="aff" rid="aff6"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-5632-1394</contrib-id><name-alternatives><name xml:lang="en"><surname>Timergaleev</surname><given-names>Rafael N.</given-names></name><name xml:lang="ru"><surname>Тимергалеев</surname><given-names>Рафаэль Наилевич</given-names></name><name xml:lang="zh"><surname>Timergaleev</surname><given-names>Rafael N.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>rafa-el99@mail.ru</email><xref ref-type="aff" rid="aff7"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-4931-0261</contrib-id><name-alternatives><name xml:lang="en"><surname>Kupriyanov</surname><given-names>Aleksandr M.</given-names></name><name xml:lang="ru"><surname>Куприянов</surname><given-names>Александр Михайлович</given-names></name><name xml:lang="zh"><surname>Kupriyanov</surname><given-names>Aleksandr M.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>mgaine@mail.ru</email><xref ref-type="aff" rid="aff8"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-8268-2511</contrib-id><name-alternatives><name xml:lang="en"><surname>Chuprina</surname><given-names>Anastasiia A.</given-names></name><name xml:lang="ru"><surname>Чуприна</surname><given-names>Анастасия Александровна</given-names></name><name xml:lang="zh"><surname>Chuprina</surname><given-names>Anastasiia A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Chuprinik5@gmail.com</email><xref ref-type="aff" rid="aff9"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-1878-2739</contrib-id><name-alternatives><name xml:lang="en"><surname>Aslakhanov</surname><given-names>Azamat I.</given-names></name><name xml:lang="ru"><surname>Аслаханов</surname><given-names>Азамат Ибрагимович</given-names></name><name xml:lang="zh"><surname>Aslakhanov</surname><given-names>Azamat I.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>azamat.aslakhanov@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0005-4056-346X</contrib-id><name-alternatives><name xml:lang="en"><surname>Veremiychuk</surname><given-names>Victoria Yu.</given-names></name><name xml:lang="ru"><surname>Веремийчук</surname><given-names>Виктория Юрьевна</given-names></name><name xml:lang="zh"><surname>Veremiychuk</surname><given-names>Victoria Yu.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>dr.veremiychuk_vu@mail.ru</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-2472-4828</contrib-id><name-alternatives><name xml:lang="en"><surname>Maryin</surname><given-names>Anton O.</given-names></name><name xml:lang="ru"><surname>Марьин</surname><given-names>Антон Олегович</given-names></name><name xml:lang="zh"><surname>Maryin</surname><given-names>Anton O.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>antonmarin241@mail.ru</email><xref ref-type="aff" rid="aff10"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">North Ossetian State Medical Academy</institution></aff><aff><institution xml:lang="ru">Северо-Осетинская государственная медицинская академия</institution></aff><aff><institution xml:lang="zh">North Ossetian State Medical Academy</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Stavropol State Medical University</institution></aff><aff><institution xml:lang="ru">Ставропольский государственный медицинский университет</institution></aff><aff><institution xml:lang="zh">Stavropol State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Ryazan State Medical University named after I.P. Pavlov</institution></aff><aff><institution xml:lang="ru">Рязанский государственный медицинский университет им. И.П. Павлова</institution></aff><aff><institution xml:lang="zh">Ryazan State Medical University named after I.P. Pavlov</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Pavlov First Saint Petersburg State Medical University</institution></aff><aff><institution xml:lang="ru">Первый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова</institution></aff><aff><institution xml:lang="zh">Pavlov First Saint Petersburg State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff5"><aff><institution xml:lang="en">Privolzhsky Research Medical University</institution></aff><aff><institution xml:lang="ru">Приволжский исследовательский медицинский университет</institution></aff><aff><institution xml:lang="zh">Privolzhsky Research Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff6"><aff><institution xml:lang="en">Sechenov First Moscow State Medical University</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет им. И.М. Сеченова</institution></aff><aff><institution xml:lang="zh">Sechenov First Moscow State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff7"><aff><institution xml:lang="en">Kazan Federal University</institution></aff><aff><institution xml:lang="ru">Казанский федеральный университет</institution></aff><aff><institution xml:lang="zh">Kazan Federal University</institution></aff></aff-alternatives><aff-alternatives id="aff8"><aff><institution xml:lang="en">Krasnoyarsk State Medical University</institution></aff><aff><institution xml:lang="ru">Красноярский государственный медицинский университет</institution></aff><aff><institution xml:lang="zh">Krasnoyarsk State Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff9"><aff><institution xml:lang="en">Vernadsky Crimean Federal University</institution></aff><aff><institution xml:lang="ru">Крымский федеральный университет им. В.И. Вернадского</institution></aff><aff><institution xml:lang="zh">Vernadsky Crimean Federal University</institution></aff></aff-alternatives><aff-alternatives id="aff10"><aff><institution xml:lang="en">Ulyanovsk State University</institution></aff><aff><institution xml:lang="ru">Ульяновский государственный университет</institution></aff><aff><institution xml:lang="zh">Ulyanovsk State University</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-05-21" publication-format="electronic"><day>21</day><month>05</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-08-16" publication-format="electronic"><day>16</day><month>08</month><year>2025</year></pub-date><volume>24</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><issue-title xml:lang="zh"/><fpage>235</fpage><lpage>253</lpage><history><date date-type="received" iso-8601-date="2025-03-30"><day>30</day><month>03</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-04-03"><day>03</day><month>04</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2025,</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://eco-vector.com/for_authors.php#07</ali:license_ref></license></permissions><self-uri xlink:href="https://rjpbr.com/1681-3456/article/view/677844">https://rjpbr.com/1681-3456/article/view/677844</self-uri><abstract xml:lang="en"><p>Alzheimer disease (AD) is the most common form of dementia, characterized by progressive cognitive decline, memory impairment, synaptic dysfunction, and neurodegeneration. The available treatment options primarily aim to temporarily alleviate symptoms without addressing the underlying pathogenetic mechanisms. In recent years, there has been an increased focus on non-pharmacological approaches that may slow the progression of AD and improve cognitive function. One promising area is the investigation of irisin, a myokine released in response to physical activity that has been shown in recent studies to exert multifaceted neuroprotective effects. Irisin regulates brain-derived neurotrophic factor expression, activates neurogenesis, improves insulin sensitivity and energy metabolism, and reduces neuroinflammation and oxidative stress. Preclinical studies have demonstrated that irisin improves memory performance, spatial learning, and synaptic plasticity in animal models of AD. Moreover, physical activity that promotes irisin secretion has been shown to improve cognitive function and overall well-being in patients with AD. This review summarizes current data on the mechanisms of irisin action and its role in the pathogenesis and treatment of AD. The review emphasizes the need for further research, particularly studies on pharmacological modulation of irisin and the integration of physical exercise into comprehensive treatment strategies. Irisin is considered a promising target for developing novel prevention and treatment strategies in AD.</p></abstract><trans-abstract xml:lang="ru"><p>Болезнь Альцгеймера (БА) — это наиболее распространённая форма деменции, характеризующаяся прогрессирующей потерей когнитивных функций, ухудшением памяти, синаптической дисфункцией и нейродегенерацией. В настоящее время существующие методы лечения в основном направлены на временное облегчение симптомов, не влияя на ключевые механизмы патогенеза заболевания. В последние годы особое внимание уделяется поиску немедикаментозных подходов, способных замедлить прогрессирование БА и улучшить когнитивное функционирование. Одним из таких перспективных направлений является изучение роли иризина — миокина, выделяемого в ответ на физическую активность, который, как показали недавние исследования, обладает многоуровневым нейропротекторным действием. Иризин участвует в регуляции экспрессии нейротрофического фактора мозга, активирует нейрогенез, улучшает инсулиновую чувствительность и энергетический метаболизм, снижает уровень нейровоспаления и окислительного стресса. Доклинические исследования демонстрируют, что введение иризина улучшает показатели памяти, пространственного обучения и синаптической пластичности у животных с моделью БА. Кроме того, физическая активность, стимулирующая секрецию иризина, показала положительное влияние на когнитивные функции и общее самочувствие пациентов с БА. Обзор обобщает современные данные о механизмах действия иризина и его роли в патогенезе и терапии БА. Обоснована необходимость дальнейших клинических исследований, направленных на изучение фармакологической модуляции иризина, а также интеграции физических упражнений в комплексные лечебные программы. Иризин рассматривается как многообещающая мишень для создания новых стратегий профилактики и лечения БА.</p></trans-abstract><trans-abstract xml:lang="zh"><p>阿尔茨海默病（Alzheimer disease, AD）是最常见的痴呆类型，其特征包括认知功能逐渐丧失、记忆障碍、突触功能受损和神经退行性变。目前现有治疗方法多以缓解症状为主，难以干预疾病的核心发病机制。近年来，非药物干预手段日益受到关注，旨在延缓AD的进程并改善患者认知功能。其中一个前景广阔的方向是对鸢尾素（irisin）作用的研究。这是一种在体育锻炼反应中由骨骼肌分泌的肌源因子，最新研究表明其具有多层面的神经保护效应。鸢尾素参与调控脑源性神经营养因子的表达，激活神经发生，改善胰岛素敏感性与能量代谢，并降低神经炎症和氧化应激水平。临床前研究表明，在AD动物模型中给予鸢尾素可改善记忆能力、空间学习和突触可塑性。此外，体育锻炼促进鸢尾素分泌，也被证明有助于改善AD患者的认知状态与整体健康状况。本文综述了鸢尾素的作用机制及其在AD的发病机制与治疗中的作用。强调需进一步进行临床研究，探讨鸢尾素的药理调控方式，并推动将体育锻炼纳入综合治疗方案。鸢肌素被视为开发AD防治新策略的潜在关键靶点。</p></trans-abstract><kwd-group xml:lang="en"><kwd>Alzheimer disease</kwd><kwd>irisin</kwd><kwd>BDNF</kwd><kwd>neurogenesis</kwd><kwd>neuroinflammation</kwd><kwd>insulin resistance</kwd><kwd>glucose metabolism</kwd><kwd>physical activity</kwd><kwd>myokines</kwd><kwd>neuroprotection</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>болезнь Альцгеймера</kwd><kwd>иризин</kwd><kwd>BDNF</kwd><kwd>нейрогенез</kwd><kwd>нейровоспаление</kwd><kwd>инсулинорезистентность</kwd><kwd>глюкозный метаболизм</kwd><kwd>физическая активность</kwd><kwd>миокины</kwd><kwd>нейропротекция</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>阿尔茨海默病</kwd><kwd>鸢尾素</kwd><kwd>脑源性神经营养因子</kwd><kwd>神经发生</kwd><kwd>神经炎症</kwd><kwd>胰岛素抵抗</kwd><kwd>葡萄糖代谢</kwd><kwd>体育锻炼</kwd><kwd>肌源因子</kwd><kwd>神经保护</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Tappakhov AA, Nikolaeva TYa, Popova TE, Shnayder NA. Diﬃculties in diagnosing atypical variants of Alzheimer’s disease. Russian neurological journal. 2021;26(5):16–23. doi: 10.30629/2658-7947-2021-26-5-16-23 EDN: FNJALQ</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Odinak MM, Litvinenko IV, Emelin AIu, et al. Pathomorphological changes in dementia: a priority of domestic researchers. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(6-2):28–34. doi: 10.17116/jnevro20161166228-34 EDN: WMWLST</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Kolykhalov IV. Current approaches to optimize treatment of dementia and Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(6):87–92. doi: 10.17116/jnevro20161166187-92 EDN: WDCPQV</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Khasanova GR, Muzaffarova MSh. Risk factors for the alzheimer’s disease. Systematic review and meta-analysis. Fundamental and Clinical Medicine. 2023;8(4):101–114. doi: 10.23946/2500-0764-2023-8-4-101-114 EDN: HFNWXA</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Ishmuratova AN, Abramov MA, Kuznetsov KO, et al. The role of antidiabetic drugs in the treatment of Alzheimer’s disease: systematic review. Problems of Endocrinology. 2023;69(5):73–83. doi: 10.14341/probl13183 EDN: RHLRQI</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Vorobev SV, Emelin AYu, Yanishevskij SN. The evolution of ideas about the treatment of Alzheimer’s disease: from the past to the present day. Russian neurological journal. 2022;27(1):5–15. doi: 10.30629/2658-7947-2022-27-1-5-15 EDN: FHDDKL</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Rivers-Auty J, Mather AE, Peters R, et al. Anti-inflammatories in Alzheimer’s disease-potential therapy or spurious correlate? Brain Commun. 2020;2(2):fcaa109. doi: 10.1093/braincomms/fcaa109</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Ratne N, Jari S, Tadas M, et al. Neurobiological role and therapeutic potential of exercise-induced irisin in Alzheimer’s disease management. Ageing Res Rev. 2025;105:102687. doi: 10.1016/j.arr.2025.102687</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bykov NA. The effect of physical activity on the human brain. Innovative science. 2024;7(2):26–29. EDN: EFPLEG</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Walsh JJ, Tschakovsky ME. Exercise and circulating BDNF: Mechanisms of release and implications for the design of exercise interventions. Appl Physiol Nutr Metab. 2018;43(11):1095–1104. doi: 10.1139/apnm-2018-0192</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Mamutova EM, Sheptulina AF, Timofeev YuS, et al. Serum concentrations of irisin, erythroferrone, myostatin and interleukin-6 in obese patients depending on the presence of sarcopenia. Russian Journal of Preventive Medicine. 2025;28(2):67–73. doi: 10.17116/profmed20252802167 EDN: YJNAVC</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Yardimci A, Ertugrul NU, Ozgen A, et al. Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study. Neurosci Lett. 2023;806:137245. doi: 10.1016/j.neulet.2023.137245</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Tan ZX, Dong F, Wu LY, et al. The Beneficial Role of Exercise on Treating Alzheimer’s Disease by Inhibiting β-Amyloid Peptide. Mol Neurobiol. 2021;58(11):5890–5906. doi: 10.1007/s12035-021-02514-7</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Andyarzhanova EA, Voronina TA. Irisin at the Crossroad of Autophagy and BNDF Signaling for Neuroplasticity Regulation. Nejrohimiâ. 2023;40(2):132–145 doi: 10.31857/S1027813323020036 EDN: UCLCIM</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Zhang H, Jiang X, Ma L, et al. Role of Aβ in Alzheimer’s-related synaptic dysfunction. Front Cell Dev Biol. 2022;10:964075. doi: 10.3389/fcell.2022.964075</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Kuznetsov KO, Khaidarova RR, Khabibullina RH, et al. Testosterone and Alzheimer’s disease. Problems of Endocrinology. 2022;68(5):97–107. doi: 10.14341/probl13136 EDN: RWUZOC</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Vasenina EE, Levin OS, Sonin AG. Modern trends in epidemiology of dementia and management of patients with cognitive impairment. S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(6–2): 87–95. doi: 10.17116/jnevro20171176287-95 EDN: ZGYWOX</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Pless A, Ware D, Saggu S, et al. Understanding neuropsychiatric symptoms in Alzheimer’s disease: challenges and advances in diagnosis and treatment. Front Neurosci. 2023;17:1263771. doi: 10.3389/fnins.2023.1263771</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Giau VV, Senanarong V, Bagyinszky E, et al. Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer’s Disease. Int J Mol Sci. 2019;20(6):1514. doi: 10.3390/ijms20061514</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Volobuev AN, Pyatin VF, Romanchuk NP, Aleksandrova NN. Genotypes and phenotypes of Alzheimer’s disease. Science and Innovations in Medicine. 2018;3(3):17–20. doi: 10.35693/2500-1388-2018-0-3-17-20 EDN: YPEKJN</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci. 2015;9:124. doi: 10.3389/fncel.2015.00124</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Schmalhausen EV, Medvedeva MV, Muronetz VI. Glyceraldehyde-3-phosphate dehydrogenase is involved in the pathogenesis of Alzheimer’s disease. Arch Biochem Biophys. 2024;758:110065. doi: 10.1016/j.abb.2024.110065</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Gao Y, Tan L, Yu JT, Tan L. Tau in Alzheimer’s Disease: Mechanisms and Therapeutic Strategies. Curr Alzheimer Res. 2018;15(3):283–300. doi: 10.2174/1567205014666170417111859</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Onyango IG, Jauregui GV, Čarná M, et al. Neuroinflammation in Alzheimer’s Disease. Biomedicines. 2021;9(5):524. doi: 10.3390/biomedicines9050524</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Ahmad SR, Zeyaullah M, AlShahrani AM, et al. Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders. Front Biosci (Landmark Ed). 2024;29(4):142. doi: 10.31083/j.fbl2904142</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Sirisi S, Sánchez-Aced É, Belbin O, Lleó A. APP dyshomeostasis in the pathogenesis of Alzheimer’s disease: implications for current drug targets. Alzheimers Res Ther. 2024;16(1):144. doi: 10.1186/s13195-024-01504-w</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Kukharskiĭ MS, Ovchinnikov RK, Bachurin SO. Molecular aspects of the pathogenesis and current approaches to pharmacological correction of Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2015;115(6):103–114. doi: 10.17116/jnevro20151156103-114 EDN: UKQWIN</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Penke B, Bogár F, Fülöp L. β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View. Molecules. 2017;22(10):1692. doi: 10.3390/molecules22101692</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Wang R, Zhang Y, Li J, Zhang C. Resveratrol ameliorates spatial learning memory impairment induced by Aβ1-42 in rats. Neuroscience. 2017;344:39–47. doi: 10.1016/j.neuroscience.2016.08.051</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Sun X, Chen WD, Wang YD. β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol. 2015;6:221. doi: 10.3389/fphar.2015.00221</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Hussain T, Tan B, Yin Y, et al. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev. 2016;2016:7432797. doi: 10.1155/2016/7432797</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Ahmad MH, Fatima M, Mondal AC. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease: Rational insights for the therapeutic approaches. J Clin Neurosci. 2019;59:6–11. doi: 10.1016/j.jocn.2018.10.034</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Kempuraj D, Thangavel R, Natteru PA, et al. Neuroinflammation Induces Neurodegeneration. J Neurol Neurosurg Spine. 2016;1(1):1003.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Lian H, Zheng H. Signaling pathways regulating neuron-glia interaction and their implications in Alzheimer’s disease. J Neurochem. 2016;136(3):475–91. doi: 10.1111/jnc.13424</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>de Oliveira J, Kucharska E, Garcez ML, et al. Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings. Cells. 2021;10(10):2581. doi: 10.3390/cells10102581</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Metaxas A, Kempf SJ. Neurofibrillary tangles in Alzheimer’s disease: elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics. Neural Regen Res. 2016;11(10):1579–1581. doi: 10.4103/1673-5374.193234</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Zhang M, Ganz AB, Rohde S, et al. Resilience and resistance to the accumulation of amyloid plaques and neurofibrillary tangles in centenarians: An age-continuous perspective. Alzheimers Dement. 2023;19(7):2831–2841. doi: 10.1002/alz.12899</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Richter-Landsberg C. Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration. Biol Chem. 2016;397(3):185–94. doi: 10.1515/hsz-2015-0157</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Gao Y, Tan L, Yu JT, Tan L. Tau in Alzheimer’s Disease: Mechanisms and Therapeutic Strategies. Curr Alzheimer Res. 2018;15(3):283–300. doi: 10.2174/1567205014666170417111859</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Cai Q, Tammineni P. Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease. J Alzheimers Dis. 2017;57(4):1087–1103. doi: 10.3233/JAD-160726</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>de Calignon A, Spires-Jones TL, Pitstick R, et al. Tangle-bearing neurons survive despite disruption of membrane integrity in a mouse model of tauopathy. J Neuropathol Exp Neurol. 2009;68(7):757–61. doi: 10.1097/NEN.0b013e3181a9fc66</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Kaur D, Sharma V, Deshmukh R. Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease. Inflammopharmacology. 2019;27(4):663–677. doi: 10.1007/s10787-019-00580-x</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Laurent C, Buée L, Blum D. Tau and neuroinflammation: What impact for Alzheimer’s Disease and Tauopathies? Biomed J. 2018;41(1):21–33. doi: 10.1016/j.bj.2018.01.003</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Saroja SR, Sharma A, Hof PR, Pereira AC. Differential expression of tau species and the association with cognitive decline and synaptic loss in Alzheimer’s disease. Alzheimers Dement. 2022;18(9):1602–1615. doi: 10.1002/alz.12518</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol. 2009;68(1):1–14. doi: 10.1097/NEN.0b013e3181919a48</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Leveille E, Ross OA, Gan-Or Z. Tau and MAPT genetics in tauopathies and synucleinopathies. Parkinsonism Relat Disord. 2021;90:142–154. doi: 10.1016/j.parkreldis.2021.09.008</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Sharma K, Pradhan S, Duffy LK, et al. Role of Receptors in Relation to Plaques and Tangles in Alzheimer’s Disease Pathology. Int J Mol Sci. 2021;22(23):12987. doi: 10.3390/ijms222312987</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Kuzmin EA, Shamitko ZV, Piavchenko GA, et al. Biomarkers of neuroinflammation in the diagnosis of traumatic brain injury and neurodegenerative diseases: a literature review. Sechenov Medical Journal. 2024;15(1):20–35. doi: 10.47093/2218-7332.2024.15.1.20-35 EDN: PWFHHW</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Shen XN, Niu LD, Wang YJ, et al. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies. J Neurol Neurosurg Psychiatry. 2019;90(5):590–598. doi: 10.1136/jnnp-2018-319148</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Webers A, Heneka MT, Gleeson PA. The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer’s disease. Immunol Cell Biol. 2020 ;98(1):28–41. doi: 10.1111/imcb.12301</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Mittal M, Siddiqui MR, Tran K, et al. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126–67. doi: 10.1089/ars.2012.5149</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med. 2015;3(10):136. doi: 10.3978/j.issn.2305-5839.2015.03.49</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Jensen CJ, Massie A, De Keyser J. Immune players in the CNS: the astrocyte. J Neuroimmune Pharmacol. 2013;8(4):824–39. doi: 10.1007/s11481-013-9480-6</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020;9(1):42. doi: 10.1186/s40035-020-00221-2</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Sheng WS, Hu S, Feng A, Rock RB. Reactive oxygen species from human astrocytes induced functional impairment and oxidative damage. Neurochem Res. 2013;38(10):2148–59. doi: 10.1007/s11064-013-1123-z</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Avila-Muñoz E, Arias C. When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer’s disease. Ageing Res Rev. 2014;18:29–40. doi: 10.1016/j.arr.2014.07.004</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Phillips EC, Croft CL, Kurbatskaya K, et al. Astrocytes and neuroinflammation in Alzheimer’s disease. Biochem Soc Trans. 2014;42(5):1321–5. doi: 10.1042/BST20140155</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther. 2021;27(1):36–47. doi: 10.1111/cns.13569</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021;17(3):157–172. doi: 10.1038/s41582-020-00435-y</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Sharma VK, Singh TG. Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer’s disease. Life Sci. 2020;262:118401. doi: 10.1016/j.lfs.2020.118401</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Berlanga-Acosta J, Guillén-Nieto G, Rodríguez-Rodríguez N, et al. Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review. Front Endocrinol (Lausanne). 2020;11:560375. doi: 10.3389/fendo.2020.560375</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Ochiai T, Sano T, Nagayama T, et al. Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2021;159:105510. doi: 10.1016/j.nbd.2021.105510</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Smailovic U, Koenig T, Savitcheva I, et al. Regional Disconnection in Alzheimer Dementia and Amyloid-Positive Mild Cognitive Impairment: Association Between EEG Functional Connectivity and Brain Glucose Metabolism. Brain Connect. 2020;10(10):555–565. doi: 10.1089/brain.2020.0785</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Gratuze M, Joly-Amado A, Vieau D, Buée L, Blum D. Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies? Neuroendocrinology. 2018;107(2):181–195. doi: 10.1159/000487641</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Li X, Song D, Leng SX. Link between type 2 diabetes and Alzheimer’s disease: from epidemiology to mechanism and treatment. Clin Interv Aging. 2015;10:549–60. doi: 10.2147/CIA.S74042</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Neth BJ, Craft S. Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages. Front Aging Neurosci. 2017;9:345. doi: 10.3389/fnagi.2017.00345</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Luchsinger JA, Patel B, Tang MX, et al. Measures of adiposity and dementia risk in elderly persons. Arch Neurol. 2007;64(3):392–8. doi: 10.1001/archneur.64.3.392</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Bosco D, Fava A, Plastino M, et al. Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. J Cell Mol Med. 2011;15(9):1807–21. doi: 10.1111/j.1582-4934.2011.01318.x</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Tsoriev TT, White ZhE, Rozhinskaya LYa. The role of myokines interstitial interaction and regulation of metabolism: a review of literature. Osteoporosis and Bone Diseases. 2016;19(1):28–34. doi: 10.14341/osteo2016128-34 EDN: XQVZDL</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Kornel A, Den Hartogh DJ, Klentrou P, Tsiani E. Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence. Int J Mol Sci. 2021;22(17):9136. doi: 10.3390/ijms22179136</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Liu S, Cui F, Ning K, et al. Role of irisin in physiology and pathology. Front Endocrinol (Lausanne). 2022;13:962968. doi: 10.3389/fendo.2022.962968</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Dinas PC, Lahart IM, Timmons JA, et al. Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Ιrisin and UCP1 of white adipocytes in humans: A systematic review. F1000Res. 2017;6:286. doi: 10.12688/f1000research.11107.2</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Hofmann T, Elbelt U, Stengel A. Irisin as a muscle-derived hormone stimulating thermogenesis--a critical update. Peptides. 2014;54:89–100. doi: 10.1016/j.peptides.2014.01.016</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Zhang Y, Li R, Meng Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514–25. doi: 10.2337/db13-1106</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Kim SH, Plutzky J. Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders. Diabetes Metab J. 2016;40(1):12–21. doi: 10.4093/dmj.2016.40.1.12</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Duan H, Ma B, Ma X, et al. Anti-diabetic activity of recombinant irisin in STZ-induced insulin-deficient diabetic mice. Int J Biol Macromol. 2016;84:457–63. doi: 10.1016/j.ijbiomac.2015.12.049</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Dong J, Dong Y, Dong Y, et al. Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated cross talk between muscle and adipose tissues. Int J Obes (Lond). 2016;40(3):434–442. doi: 10.1038/ijo.2015.200</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Ozcan S, Ulker N, Bulmus O, et al. The modulatory effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats. Arch Physiol Biochem. 2022;128(3):724–731. doi: 10.1080/13813455.2020.1722706</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Flori L, Testai L, Calderone V. The “irisin system”: From biological roles to pharmacological and nutraceutical perspectives. Life Sci. 2021;267:118954. doi: 10.1016/j.lfs.2020.118954</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Perakakis N, Triantafyllou GA, Fernández-Real JM, et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017;13(6):324–337. doi: 10.1038/nrendo.2016.221</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med. 2019;25(1):165–175. doi: 10.1038/s41591-018-0275-4</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Waseem R, Shamsi A, Mohammad T, et al. Multispectroscopic and Molecular Docking Insight into Elucidating the Interaction of Irisin with Rivastigmine Tartrate: A Combinational Therapy Approach to Fight Alzheimer’s Disease. ACS Omega. 2021;6(11):7910–7921. doi: 10.1021/acsomega.1c00517</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Lourenco MV, Ribeiro FC, Sudo FK, et al. Cerebrospinal fluid irisin correlates with amyloid-β, BDNF, and cognition in Alzheimer’s disease. Alzheimers Dement (Amst). 2020;12(1):e12034. doi: 10.1002/dad2.12034</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Huang X, Wang J, Zhang S, et al. Plasma BDNF/Irisin Ratio Associates with Cognitive Function in Older People. J Alzheimers Dis. 2024;99(4):1261–1271. doi: 10.3233/JAD-231347</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Bretland KA, Lin L, Bretland KM, et al. Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice. Neuropathol Appl Neurobiol. 2021;47(7):967–978. doi: 10.1111/nan.12711</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Dehghan F, Zamani S, Barreiro C, Jami MS. Irisin injection mimics exercise effects on the brain proteome. Eur J Neurosci. 2021;54(10):7422–7441. doi: 10.1111/ejn.15493</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Slate-Romano JJ, Yano N, Zhao TC. Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome. Mol Cell Endocrinol. 2022;552:111676. doi: 10.1016/j.mce.2022.111676</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Korta P, Pocheć E, Mazur-Biały A. Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases. Medicina (Kaunas). 2019;55(8):485. doi: 10.3390/medicina55080485</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Sale A, Berardi N, Maffei L. Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol Rev. 2014;94(1):189–234. doi: 10.1152/physrev.00036.2012</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Ng TKS, Ho CSH, Tam WWS, et al. Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis. Int J Mol Sci. 2019;20(2):257. doi: 10.3390/ijms20020257</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol. 2014;220:223–50. doi: 10.1007/978-3-642-45106-5_9</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Yuan C, Guo X, Zhou Q, et al. OAB-14, a bexarotene derivative, improves Alzheimer’s disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):161–180. doi: 10.1016/j.bbadis.2018.10.028</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Kheiri G, Dolatshahi M, Rahmani F, Rezaei N. Role of p38/MAPKs in Alzheimer’s disease: implications for amyloid beta toxicity targeted therapy. Rev Neurosci. 2018;30(1):9–30. doi: 10.1515/revneuro-2018-0008</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>Jodeiri Farshbaf M, Alviña K. Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin. Front Aging Neurosci. 2021;13:649929. doi: 10.3389/fnagi.2021.649929</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Wrann CD, White JP, Salogiannnis J, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013;18(5):649–59. doi: 10.1016/j.cmet.2013.09.008</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Aimone JB, Li Y, Lee SW, et al. Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev. 2014;94(4):991–1026. doi: 10.1152/physrev.00004.2014</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>Jurkowski MP, Bettio L, K Woo E, et al. Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain. Front Cell Neurosci. 2020;14:576444. doi: 10.3389/fncel.2020.576444</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>Winner B, Regensburger M, Schreglmann S, et al. Role of α-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus. J Neurosci. 2012;32(47):16906–16. doi: 10.1523/JNEUROSCI.2723-12.2012</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>Rodriguez-Ortiz CJ, Baglietto-Vargas D, Martinez-Coria H, et al. Upregulation of miR-181 decreases c-Fos and SIRT-1 in the hippocampus of 3xTg-AD mice. J Alzheimers Dis. 2014;42(4):1229–38. doi: 10.3233/JAD-140204</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>Rodríguez JJ, Jones VC, Tabuchi M, et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer’s disease. PLoS One. 2008;3(8):e2935. doi: 10.1371/journal.pone.0002935</mixed-citation></ref><ref id="B101"><label>101.</label><mixed-citation>Kim OY, Song J. The Role of Irisin in Alzheimer’s Disease. J Clin Med. 2018;7(11):407. doi: 10.3390/jcm7110407</mixed-citation></ref><ref id="B102"><label>102.</label><mixed-citation>Sadier NS, El Hajjar F, Al Sabouri AAK, et al. Irisin: An unveiled bridge between physical exercise and a healthy brain. Life Sci. 2024;339:122393. doi: 10.1016/j.lfs.2023.122393</mixed-citation></ref><ref id="B103"><label>103.</label><mixed-citation>Choi JW, Jo SW, Kim DE, et al. Aerobic exercise attenuates LPS-induced cognitive dysfunction by reducing oxidative stress, glial activation, and neuroinflammation. Redox Biol. 2024;71:103101. doi: 10.1016/j.redox.2024.103101</mixed-citation></ref><ref id="B104"><label>104.</label><mixed-citation>Leger C, Quirié A, Méloux A, Fontanier E, Chaney R, Basset C, Lemaire S, Garnier P, Prigent-Tessier A. Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin. Int J Mol Sci. 2024; 25(2):1213. doi: 10.3390/ijms25021213</mixed-citation></ref><ref id="B105"><label>105.</label><mixed-citation>de Oliveira Bristot VJ, de Bem Alves AC, Cardoso LR, et al. The Role of PGC-1α/UCP2 Signaling in the Beneficial Effects of Physical Exercise on the Brain. Front Neurosci. 2019;13:292. doi: 10.3389/fnins.2019.00292</mixed-citation></ref><ref id="B106"><label>106.</label><mixed-citation>Jodeiri Farshbaf M, Ghaedi K, Megraw TL, et al. Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders? Neuromolecular Med. 2016;18(1):1–15. doi: 10.1007/s12017-015-8370-x</mixed-citation></ref><ref id="B107"><label>107.</label><mixed-citation>Akhtar A, Sah SP. Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochem Int. 2020;135:104707. doi: 10.1016/j.neuint.2020.104707</mixed-citation></ref><ref id="B108"><label>108.</label><mixed-citation>Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res. 2017;95(4):943–972. doi: 10.1002/jnr.23777</mixed-citation></ref><ref id="B109"><label>109.</label><mixed-citation>Kyrtata N, Emsley HCA, Sparasci O, et al. A Systematic Review of Glucose Transport Alterations in Alzheimer’s Disease. Front Neurosci. 2021;15:626636. doi: 10.3389/fnins.2021.626636</mixed-citation></ref><ref id="B110"><label>110.</label><mixed-citation>Tang H, Yu R, Liu S, et al. Irisin Inhibits Hepatic Cholesterol Synthesis via AMPK-SREBP2 Signaling. EBioMedicine. 2016;6:139–148. doi: 10.1016/j.ebiom.2016.02.041</mixed-citation></ref><ref id="B111"><label>111.</label><mixed-citation>Kurdiova T, Balaz M, Vician M, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol. 2014;592(5):1091–107. doi: 10.1113/jphysiol.2013.264655</mixed-citation></ref><ref id="B112"><label>112.</label><mixed-citation>Shen S, Liao Q, Chen X, et al. The role of irisin in metabolic flexibility: Beyond adipose tissue browning. Drug Discov Today. 2022;27(8):2261–2267. doi: 10.1016/j.drudis.2022.03.019</mixed-citation></ref><ref id="B113"><label>113.</label><mixed-citation>Lee HJ, Lee JO, Kim N, et al. Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK. Mol Endocrinol. 2015;29(6):873–81. doi: 10.1210/me.2014-1353</mixed-citation></ref><ref id="B114"><label>114.</label><mixed-citation>Steinberg GR, Hardie DG. New insights into activation and function of the AMPK. Nat Rev Mol Cell Biol. 2023;24(4):255–272. doi: 10.1038/s41580-022-00547-x</mixed-citation></ref><ref id="B115"><label>115.</label><mixed-citation>Qi JY, Yang LK, Wang XS, et al. Irisin: A promising treatment for neurodegenerative diseases. Neuroscience. 2022;498:289–299. doi: 10.1016/j.neuroscience.2022.07.018</mixed-citation></ref><ref id="B116"><label>116.</label><mixed-citation>Madhu LN, Somayaji Y, Shetty AK. Promise of irisin to attenuate cognitive dysfunction in aging and Alzheimer’s disease. Ageing Res Rev. 2022;78:101637. doi: 10.1016/j.arr.2022.101637</mixed-citation></ref><ref id="B117"><label>117.</label><mixed-citation>Mohammadi S, Oryan S, Komaki A, et al. Effects of intra-dentate gyrus microinjection of myokine irisin on long-term potentiation in male rats. Arq Neuropsiquiatr. 2019;77(12):881–887. doi: 10.1590/0004-282X20190184</mixed-citation></ref><ref id="B118"><label>118.</label><mixed-citation>Landry T, Huang H. Mini review: The relationship between energy status and adult hippocampal neurogenesis. Neurosci Lett. 2021;765:136261. doi: 10.1016/j.neulet.2021.136261</mixed-citation></ref><ref id="B119"><label>119.</label><mixed-citation>Bettinetti-Luque M, Trujillo-Estrada L, Garcia-Fuentes E, et al. Adipose tissue as a therapeutic target for vascular damage in Alzheimer’s disease. Br J Pharmacol. 2024;181(6):840–878. doi: 10.1111/bph.16243</mixed-citation></ref><ref id="B120"><label>120.</label><mixed-citation>Wang Y, Tian M, Tan J, et al. Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice. J Neuroinflammation. 2022;19(1):82. doi: 10.1186/s12974-022-02438-6</mixed-citation></ref><ref id="B121"><label>121.</label><mixed-citation>Zhang X, Xu S, Hu Y, et al. Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson’s disease. NPJ Parkinsons Dis. 2023;9(1):13. doi: 10.1038/s41531-023-00453-9</mixed-citation></ref><ref id="B122"><label>122.</label><mixed-citation>Zhang F, Hou G, Hou G, et al. Serum Irisin as a Potential Biomarker for Cognitive Decline in Vascular Dementia. Front Neurol. 2021;12:755046. doi: 10.3389/fneur.2021.755046</mixed-citation></ref><ref id="B123"><label>123.</label><mixed-citation>Jin Z, Zhang Z, Ke J, Wang Y, Wu H. Exercise-Linked Irisin Prevents Mortality and Enhances Cognition in a Mice Model of Cerebral Ischemia by Regulating Klotho Expression. Oxid Med Cell Longev. 2021;2021:1697070. doi: 10.1155/2021/1697070</mixed-citation></ref><ref id="B124"><label>124.</label><mixed-citation>Çalık M, Sengul Y, Mail GZ, et al. Association between serum irisin concentration and ischemic stroke: From etiology to clinic. J Med Biochem. 2022;41(4):534–539. doi: 10.5937/jomb0-36681</mixed-citation></ref><ref id="B125"><label>125.</label><mixed-citation>Waseem R, Shamsi A, Khan T, et al. Characterization of advanced glycation end products and aggregates of irisin: Multispectroscopic and microscopic approaches. J Cell Biochem. 2023;124(1):156–168. doi: 10.1002/jcb.30353</mixed-citation></ref><ref id="B126"><label>126.</label><mixed-citation>Rody T, De Amorim JA, De Felice FG. The emerging neuroprotective roles of exerkines in Alzheimer’s disease. Front Aging Neurosci. 2022;14:965190. doi: 10.3389/fnagi.2022.965190</mixed-citation></ref><ref id="B127"><label>127.</label><mixed-citation>Kales HC, Lyketsos CG, Miller EM, Ballard C. Management of behavioral and psychological symptoms in people with Alzheimer’s disease: an international Delphi consensus. Int Psychogeriatr. 2019;31(1):83–90. doi: 10.1017/S1041610218000534</mixed-citation></ref><ref id="B128"><label>128.</label><mixed-citation>Posadzki P, Pieper D, Bajpai R, et al. Exercise/physical activity and health outcomes: an overview of Cochrane systematic reviews. BMC Public Health. 2020;20(1):1724. doi: 10.1186/s12889-020-09855-3</mixed-citation></ref><ref id="B129"><label>129.</label><mixed-citation>Kaloğlu HA, Örsel S, Erzin G. Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia. Clin Psychopharmacol Neurosci. 2023;21(4):724–731. doi: 10.9758/cpn.22.1030</mixed-citation></ref><ref id="B130"><label>130.</label><mixed-citation>Zong B, Yu F, Zhang X, et al. Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems. Front Aging Neurosci. 2022;14:869507. doi: 10.3389/fnagi.2022.869507</mixed-citation></ref><ref id="B131"><label>131.</label><mixed-citation>Morelli C, Avolio E, Galluccio A, et al. Impact of Vigorous-Intensity Physical Activity on Body Composition Parameters, Lipid Profile Markers, and Irisin Levels in Adolescents: A Cross-Sectional Study. Nutrients. 2020;12(3):742. doi: 10.3390/nu12030742</mixed-citation></ref><ref id="B132"><label>132.</label><mixed-citation>Chen K, Wang K, Wang T. Protective effect of irisin against Alzheimer’s disease. Front Psychiatry. 2022;13:967683. doi: 10.3389/fpsyt.2022.967683</mixed-citation></ref></ref-list></back></article>
