<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">nnp</journal-id><journal-title-group><journal-title xml:lang="en">Neurology, Neuropsychiatry, Psychosomatics</journal-title><trans-title-group xml:lang="ru"><trans-title>Неврология, нейропсихиатрия, психосоматика</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-2711</issn><issn pub-type="epub">2310-1342</issn><publisher><publisher-name>"IMA-Press", LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14412/2074-2711-2023-1S-4-7</article-id><article-id custom-type="elpub" pub-id-type="custom">nnp-2069</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LECTURES</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЛЕКЦИЯ</subject></subj-group></article-categories><title-group><article-title>MicroRNAs as biomarkers of multiple sclerosis progression</article-title><trans-title-group xml:lang="ru"><trans-title>МикроРНК как биомаркеры прогрессирования рассеянного склероза</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8767-2958</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Баулина</surname><given-names>Н. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Baulina</surname><given-names>N. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Наталья Михайловна Баулина</p><p>117997, Москва, ул. Островитянова, 1</p></bio><bio xml:lang="en"><p>Natalia Mikhailovna Baulina</p><p>11, Ostrovityanova St., Moscow 117997</p></bio><email xlink:type="simple">tasha.baulina@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3366-4113</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Киселев</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kiselev</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>117997, Москва, ул. Островитянова, 1</p></bio><bio xml:lang="en"><p>11, Ostrovityanova St., Moscow 117997</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5321-3101</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кулакова</surname><given-names>О. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kulakova</surname><given-names>O. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>117997, Москва, ул. Островитянова, 1</p></bio><bio xml:lang="en"><p>11, Ostrovityanova St., Moscow 117997</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2676-452X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Попова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Popova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>117997, Москва, ул. Островитянова, 1</p><p>127015, Москва, ул. Писцовая, 10</p></bio><bio xml:lang="en"><p>11, Ostrovityanova St., Moscow 117997</p><p>210, Pistsovaya St., Moscow 127015</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5271-6698</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фаворова</surname><given-names>О. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Favorova</surname><given-names>O. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>117997, Москва, ул. Островитянова, 1</p></bio><bio xml:lang="en"><p>11, Ostrovityanova St., Moscow 117997</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2975-4151</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бойко</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Boyko</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>117997, Москва, ул. Островитянова, 1</p><p>117997, Москва, ул. Островитянова, 1, стр. 10</p></bio><bio xml:lang="en"><p>11, Ostrovityanova St., Moscow 117997</p><p>1, Ostrovityanova St., Build. 10, Moscow 117997</p></bio><xref ref-type="aff" rid="aff-5"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov Russian National Research Medical University, Ministry of Health of N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ГБУЗ «Городская клиническая больница №24 Департамента здравоохранения г. Москвы»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov Russian National Research Medical University, Ministry of Health of N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussia; City Clinical Hospital Twenty-Four, Moscow Healthcare Department</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov Russian National Research Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; отдел нейроиммунологии Института клинической неврологии ФГБУ&#13;
«Федеральный центр мозга и нейротехнологий» ФМБА Росии</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Department of Neuroimmunology, Institute of Clinical Neurology, Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>20</day><month>08</month><year>2023</year></pub-date><volume>15</volume><issue>0</issue><issue-title>(Suppl. 1)</issue-title><fpage>4</fpage><lpage>7</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Baulina N.M., Kiselev I.S., Kulakova O.G., Popova E.V., Favorova O.O., Boyko A.N., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Баулина Н.М., Киселев И.С., Кулакова О.Г., Попова Е.В., Фаворова О.О., Бойко А.Н.</copyright-holder><copyright-holder xml:lang="en">Baulina N.M., Kiselev I.S., Kulakova O.G., Popova E.V., Favorova O.O., Boyko A.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://nnp.ima-press.net/nnp/article/view/2069">https://nnp.ima-press.net/nnp/article/view/2069</self-uri><abstract><p>Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system. The disease is characterized by a heterogeneous clinical course, which is reflected in the fact that there are various types, such as relapsing-remitting MS (RRMS), primary and secondary progressive MS (PPMS and SPMS, respectively). Currently, there is an active search for MS biomarkers capable of predicting and assessing disease progression with high sensitivity and specificity, which would be of great benefit in determining treatment tactics and evaluating their efficacy. MicroRNAs (miRNAs) are short (21–25 nucleotides) non-coding RNA molecules that are primarily involved in post-transcriptional regulation of gene expression. miRNAs play an essential role in tissue development, homeostasis, immune system regulation, and immune cell maturation; they are also involved in the pathophysiology of MS. In addition, high hopes are pinned on miRNAs as disease biomarkers, mainly due to their stability and ability to be released from cells into the extracellular space and circulate there for a long time. The review considers published data on miRNAs in different types of MS. In the future, changes in their levels may be used to create a panel of prognostic markers for disease progression. Studies of miRNAs levels in both circulating fluids (plasma, serum, cerebrospinal fluid) and brain tissue of MS patients were reviewed. Based on the aggregated data from the studies reviewed, it can be confirmed that the accumulated data are quite sufficient to recognize that regulatory miRNAs molecules are involved in the pathophysiological mechanisms of MS progression. However, there is still a long way to go to establish a panel of circulating miRNAs that predict the rate of progression of MS.</p></abstract><trans-abstract xml:lang="ru"><p>Рассеянный склероз (РC) – аутоиммунное воспалительное нейродегенеративное заболевание центральной нервной системы. Заболевание характеризуется гетерогенностью клинического течения, что отражается в существовании его различных типов, таких как ремиттирующий РС, первично- и вторично-прогрессирующий РС. В настоящее время продолжается активный поиск биомаркеров РС, позволяющих с высокой чувствительностью и специфичностью предсказать и оценить темп прогрессирования заболевания, что существенно помогло бы в определении тактики лечения и оценке его эффективности. МикроРНК (miRNAs) представляют собой короткие (21–25 нуклеотидов) некодирующие молекулы РНК, которые в основном участвуют в посттранскрипционной регуляции экспрессии генов. МикроРНК играют существенную роль в развитии тканей, гомеостазе, регуляции иммунной системы и созревании иммунных клеток; было показано, что они вовлечены и в патофизиологию РС. Кроме того, на микроРНК возлагают большие надежды с точки зрения их использования в качестве биомаркеров заболевания, что в первую очередь обусловливается их стабильностью и возможностью высвобождаться из клеток во внеклеточное пространство и там длительно циркулировать. В статье рассмотрены опубликованные данные о микроРНК при различных формах РС, изменения в уровнях которых могут в перспективе быть использованы для составления панели прогностических маркеров прогрессирования заболевания. Проанализированы работы, посвященные изучению уровней микроРНК как в циркулирующих жидкостях (плазма, сыворотка, цереброспинальная жидкость), так и в ткани мозга больных РС. На основании совокупности рассматриваемых исследований можно констатировать, что накопленных данных вполне достаточно для утверждения, что регуляторные молекулы микроРНК участвуют в формировании патофизиологических механизмов, вовлеченных в прогрессирование РС. Однако для создания панели циркулирующих микроРНК, прогнозирующих темп прогрессирования РС, предстоит пройти еще немалый путь.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>рассеянный склероз</kwd><kwd>микроРНК</kwd><kwd>прогрессирование заболевания</kwd><kwd>биомаркер</kwd></kwd-group><kwd-group xml:lang="en"><kwd>multiple sclerosis</kwd><kwd>miRNA</kwd><kwd>disease progression</kwd><kwd>biomarker</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Gao Y, Han D, Feng J. MicroRNA in multiple sclerosis. Clin Chim Acta. 2021 May;516:92-9. doi: 10.1016/j.cca.2021.01.020. Epub 2021 Feb 2.</mixed-citation><mixed-citation xml:lang="en">Gao Y, Han D, Feng J. MicroRNA in multiple sclerosis. Clin Chim Acta. 2021 May;516:92-9. doi: 10.1016/j.cca.2021.01.020. Epub 2021 Feb 2.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018 Apr;141(4):1202-7. doi: 10.1016/j.jaci.2017.08.034. Epub 2017 Oct 23.</mixed-citation><mixed-citation xml:lang="en">Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018 Apr;141(4):1202-7. doi: 10.1016/j.jaci.2017.08.034. Epub 2017 Oct 23.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Pietrasik S, Dziedzic A, Miller E, et al. Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing-Remitting from Secondary Progressive Multiple Sclerosis. A Review. Int J Mol Sci. 2021 Nov 2;22(21):11887. doi: 10.3390/ijms222111887</mixed-citation><mixed-citation xml:lang="en">Pietrasik S, Dziedzic A, Miller E, et al. Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing-Remitting from Secondary Progressive Multiple Sclerosis. A Review. Int J Mol Sci. 2021 Nov 2;22(21):11887. doi: 10.3390/ijms222111887</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Baulina NM, Kulakova OG, Favorova OO. MicroRNAs: The Role in Autoimmune Inflammation. Acta Naturae. 2016 Jan-Mar;8(1):21-33.</mixed-citation><mixed-citation xml:lang="en">Baulina NM, Kulakova OG, Favorova OO. MicroRNAs: The Role in Autoimmune Inflammation. Acta Naturae. 2016 Jan-Mar;8(1):21-33.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Martinez B, Peplow PV. MicroRNAs in blood and cerebrospinal fluid as diagnostic biomarkers of multiple sclerosis and to monitor disease progression. Neural Regen Res. 2020 Apr;15(4):606-19. doi: 10.4103/1673-5374.266905</mixed-citation><mixed-citation xml:lang="en">Martinez B, Peplow PV. MicroRNAs in blood and cerebrospinal fluid as diagnostic biomarkers of multiple sclerosis and to monitor disease progression. Neural Regen Res. 2020 Apr;15(4):606-19. doi: 10.4103/1673-5374.266905</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Baulina N, Kulakova O, Kiselev I, et al. Immune-related miRNA expression patterns in peripheral blood mononuclear cells differ in multiple sclerosis relapse and remission. J Neuroimmunol. 2018;317:67-76. doi: 10.1016/j.jneuroim.2018.01.005</mixed-citation><mixed-citation xml:lang="en">Baulina N, Kulakova O, Kiselev I, et al. Immune-related miRNA expression patterns in peripheral blood mononuclear cells differ in multiple sclerosis relapse and remission. J Neuroimmunol. 2018;317:67-76. doi: 10.1016/j.jneuroim.2018.01.005</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Haghikia A, Haghikia A, Hellwig K, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology. 2012 Nov 27;79(22):2166-70. doi: 10.1212/WNL.0b013e3182759621. Epub 2012 Oct 17.</mixed-citation><mixed-citation xml:lang="en">Haghikia A, Haghikia A, Hellwig K, et al. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology. 2012 Nov 27;79(22):2166-70. doi: 10.1212/WNL.0b013e3182759621. Epub 2012 Oct 17.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Kramer S, Haghikia A, Bang C, et al. Elevated levels of miR-181c and miR-633 in the CSF of patients with MS: A validation study. Neurol Neuroimmunol Neuroinflamm. 2019 Oct 1;6(6):e623. doi: 10.1212/NXI.0000000000000623</mixed-citation><mixed-citation xml:lang="en">Kramer S, Haghikia A, Bang C, et al. Elevated levels of miR-181c and miR-633 in the CSF of patients with MS: A validation study. Neurol Neuroimmunol Neuroinflamm. 2019 Oct 1;6(6):e623. doi: 10.1212/NXI.0000000000000623</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Gandhi R, Healy B, Gholipour T, et al. Circulating microRNAs as biomarkers for disease staging in multiple sclerosis. Ann Neurol. 2013 Jun;73(6):729-40. doi: 10.1002/ana.23880. Epub 2013 Jul 8.</mixed-citation><mixed-citation xml:lang="en">Gandhi R, Healy B, Gholipour T, et al. Circulating microRNAs as biomarkers for disease staging in multiple sclerosis. Ann Neurol. 2013 Jun;73(6):729-40. doi: 10.1002/ana.23880. Epub 2013 Jul 8.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Park CC, Thongkham DW, Sadigh G, et al. Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T. J Neuroimaging. 2021 Mar;31(2):408-14. doi: 10.1111/jon.12822. Epub 2020 Dec 22.</mixed-citation><mixed-citation xml:lang="en">Park CC, Thongkham DW, Sadigh G, et al. Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T. J Neuroimaging. 2021 Mar;31(2):408-14. doi: 10.1111/jon.12822. Epub 2020 Dec 22.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Tripathi A, Pandit I, Perles A, et al. Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures. Ann Clin Transl Neurol. 2021 Jun;8(6):1279-91. doi: 10.1002/acn3.51365. Epub 2021 May 12.</mixed-citation><mixed-citation xml:lang="en">Tripathi A, Pandit I, Perles A, et al. Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures. Ann Clin Transl Neurol. 2021 Jun;8(6):1279-91. doi: 10.1002/acn3.51365. Epub 2021 May 12.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Fritsche L, Teuber-Hanselmann S, Soub D, et al. MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin-7. Brain Pathol. 2020 May;30(3):524-40. doi: 10.1111/bpa.12800. Epub 2019 Nov 17.</mixed-citation><mixed-citation xml:lang="en">Fritsche L, Teuber-Hanselmann S, Soub D, et al. MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin-7. Brain Pathol. 2020 May;30(3):524-40. doi: 10.1111/bpa.12800. Epub 2019 Nov 17.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Regev K, Healy BC, Khalid F, et al. Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity. JAMA Neurol. 2017 Mar 1;74(3):275-85. doi: 10.1001/jamaneurol.2016.5197</mixed-citation><mixed-citation xml:lang="en">Regev K, Healy BC, Khalid F, et al. Association Between Serum MicroRNAs and Magnetic Resonance Imaging Measures of Multiple Sclerosis Severity. JAMA Neurol. 2017 Mar 1;74(3):275-85. doi: 10.1001/jamaneurol.2016.5197</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Keller A, Leidinger P, Steinmeyer F, et al. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler. 2014 Mar;20(3):295-303. doi: 10.1177/1352458513496343. Epub 2013 Jul 8.</mixed-citation><mixed-citation xml:lang="en">Keller A, Leidinger P, Steinmeyer F, et al. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler. 2014 Mar;20(3):295-303. doi: 10.1177/1352458513496343. Epub 2013 Jul 8.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Regev K, Paul A, Healy B, et al. Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 23;3(5):e267. doi: 10.1212/NXI.0000000000000267. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2016 Oct 07;3(6):e296.</mixed-citation><mixed-citation xml:lang="en">Regev K, Paul A, Healy B, et al. Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 23;3(5):e267. doi: 10.1212/NXI.0000000000000267. Erratum in: Neurol Neuroimmunol Neuroinflamm. 2016 Oct 07;3(6):e296.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Regev K, Healy BC, Paul A, et al. Identification of MS-specific serum miRNAs in an international multicenter study. Neurol Neuroimmunol Neuroinflamm. 2018 Aug 20;5(5):e491. doi: 10.1212/NXI.0000000000000491</mixed-citation><mixed-citation xml:lang="en">Regev K, Healy BC, Paul A, et al. Identification of MS-specific serum miRNAs in an international multicenter study. Neurol Neuroimmunol Neuroinflamm. 2018 Aug 20;5(5):e491. doi: 10.1212/NXI.0000000000000491</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Morrow SA, Clift F, Devonshire V, et al. Use of natalizumab in persons with multiple sclerosis: 2022 update. Mult Scler Relat Disord. 2022 Sep;65:103995. doi: 10.1016/j.msard.2022.103995. Epub 2022 Jun 26.</mixed-citation><mixed-citation xml:lang="en">Morrow SA, Clift F, Devonshire V, et al. Use of natalizumab in persons with multiple sclerosis: 2022 update. Mult Scler Relat Disord. 2022 Sep;65:103995. doi: 10.1016/j.msard.2022.103995. Epub 2022 Jun 26.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Sharaf-Eldin WE, Kishk NA, Gad YZ, et al. Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases. J Neurol Sci. 2017 Dec 15;383:188-98. doi: 10.1016/j.jns.2017.11.014. Epub 2017 Nov 15.</mixed-citation><mixed-citation xml:lang="en">Sharaf-Eldin WE, Kishk NA, Gad YZ, et al. Extracellular miR-145, miR-223 and miR-326 expression signature allow for differential diagnosis of immune-mediated neuroinflammatory diseases. J Neurol Sci. 2017 Dec 15;383:188-98. doi: 10.1016/j.jns.2017.11.014. Epub 2017 Nov 15.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Xu B, Zhang Y, Du XF, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 2017 Jul;27(7):882-97. doi: 10.1038/cr.2017.62. Epub 2017 Apr 21.</mixed-citation><mixed-citation xml:lang="en">Xu B, Zhang Y, Du XF, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 2017 Jul;27(7):882-97. doi: 10.1038/cr.2017.62. Epub 2017 Apr 21.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017 Oct 30;7(1):14293. doi: 10.1038/s41598-017-14301-3</mixed-citation><mixed-citation xml:lang="en">Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017 Oct 30;7(1):14293. doi: 10.1038/s41598-017-14301-3</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Киселев ИС, Кулакова ОГ, Баулина НМ и др. Вариабельность гена MIR196A2 как фактор риск развития первично-прогрессирующего рассеянного склероза. Молекулярная биология. 2019;53(2):282-9. doi: 10.1134/S0026898419020071</mixed-citation><mixed-citation xml:lang="en">Kiselev IS, Kulakova OG, Baulina NM, et al. Variability of the MIR196A2 Gene as a Risk Factor in Primary-Progressive Multiple Sclerosis Development. Molekulyarnaya biologiya. 2019;53(2):282-9. doi: 10.1134/S0026898419020071 (In Russ. and Engl.).</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
