vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-27vavilov-4093Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSВлияние транспозонов на развитие болезни АльцгеймераInvolvement of transposable elements in Alzheimer’s disease pathogenesisМустафинР. Н.MustafinR. N.

Уфа

Ufa

ruji79@mail.ruХуснутдиноваЭ. К.KhusnutdinovaE. K.

Уфа

Ufa

Башкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian FederationБашкирский государственный медицинский университет; Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияBashkir State Medical University; Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesRussian Federation202411042024282228238Copyright © Мустафин Р.Н., Хуснутдинова Э.К., 20242024Мустафин Р.Н., Хуснутдинова Э.К.Mustafin R.N., Khusnutdinova E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4093

Болезнь Альцгеймера поражает в среднем 5 % населения со значительным увеличением распространенности с возрастом, что свидетельствует о возможном влиянии на данную патологию тех же механизмов, которые лежат в основе старения человека. Исследование этих механизмов перспективно для разработки эффективных методов лечения и профилактики заболевания. Возможными участниками этих механизмов являются транспозоны, которые служат драйверами эпигенетической регуляции, поскольку формируют в эволюции видоспецифические распределения генов некодирующих РНК в геноме человека. Изучение роли микро-РНК в развитии болезни Альцгеймера актуально, поскольку по результатам проведенных GWAS ассоциаций белок-кодирующих генов (APOE4, ABCA7, BIN1, CLU, CR1, PICALM, TREM2) трудно объяснить сложный патогенез заболевания. Кроме того, в различных долях головного мозга при болезни Альцгеймера были обнаружены специфические изменения экспрессии множества генов, что может быть обу словлено глобальными регуляторными изменениями под влиянием транспозонов. Действительно, экспериментальные и клинические исследования показали патологическую активацию ретроэлементов при болезни Альцгеймера. Проведенный нами анализ научной литературы в соответствии с базой данных MDTE DB (microRNAs derived from transposable elements) позволил выявить 28 различных микро-РНК, происходящих от мобильных элементов (17 – от LINE, 5 – от SINE, 4 – от HERV, 2 – от ДНК-транспозонов), экспрессия которых специфически изменяется при данном заболевании (снижается у 17 и повышается у 11 микроРНК). Экспрессия 13 из 28 микро-РНК (miR-151a, -192, -211, -28, -31, -320c, -335, -340, -378a, -511, -576, -708, -885) меняется также при старении и развитии злокачественных новообразований, что подтверждает  возможное наличие общих патогенетических механизмов. Большинство из этих микро-РНК произошли от LINE-ретроэлементов, патологическая активация которых ассоциирована со старением, канцерогенезом и болезнью Альцгеймера, что свидетельствует в пользу гипотезы о том, что в основе этих трех процессов лежит первичная дисрегуляция транспозонов, которые служат драйверами эпигенетической регуляции экспрессии генов в онтогенезе. 

Alzheimer’s disease affects an average of 5 % of the population with a significant increase in prevalence with age, suggesting that the same mechanisms that underlie aging may influence this pathology. Investigation of these mechanisms is promising for effective methods of treatment and prevention of the disease. Possible participants in these mechanisms are transposons, which serve as drivers of epigenetic regulation, since they form species-specific distributions of non-coding RNA genes in genomes in evolution. Study of miRNA involvement in Alzheimer’s disease pathogenesis is relevant, since the associations of protein-coding genes (APOE4, ABCA7, BIN1, CLU, CR1, PICALM, TREM2) with the disease revealed as a result of GWAS make it difficult to explain its complex pathogenesis. Specific expression changes of many genes were found in different brain parts of Alzheimer’s patients, which may be due to global regulatory changes under the influence of transposons. Experimental and clinical studies have shown pathological activation of retroelements in Alzheimer’s disease. Our analysis of scientific literature in accordance with MDTE DB revealed 28 miRNAs derived from transposons (17 from LINE, 5 from SINE, 4 from HERV, 2 from DNA transposons), the expression of which specifically changes in this disease (decreases in 17 and increases in 11 microRNA). Expression of 13 out of 28 miRNAs (miR-151a, -192, -211, -28, -31, -320c, -335, -340, -378a, -511, -576, -708, -885) also changes with aging and cancer development, which indicates the presence of possible common pathogenetic mechanisms. Most of these miRNAs originated from LINE retroelements, the pathological activation of which is associated with aging, carcinogenesis, and Alzheimer’s disease, which supports the hypothesis that these three processes are based on the primary dysregulation of transposons that serve as drivers of epigenetic regulation of gene expression in ontogeny.

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