Involvement of transposable elements in Alzheimer’s disease pathogenesis

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 o...

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Main Authors: R. N. Mustafin, E. K. Khusnutdinova
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2024-04-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/4093
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author R. N. Mustafin
E. K. Khusnutdinova
author_facet R. N. Mustafin
E. K. Khusnutdinova
author_sort R. N. Mustafin
collection DOAJ
description 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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publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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spelling doaj-art-3b8580f8fdaf4d1f92edfb99bb68e2dc2025-02-01T09:58:13ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592024-04-0128222823810.18699/vjgb-24-271458Involvement of transposable elements in Alzheimer’s disease pathogenesisR. N. Mustafin0E. K. Khusnutdinova1Bashkir State Medical UniversityBashkir State Medical University; Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesAlzheimer’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.https://vavilov.elpub.ru/jour/article/view/4093alzheimer’s diseasecarcinogenesismirnaagingtransposonsretroelements
spellingShingle R. N. Mustafin
E. K. Khusnutdinova
Involvement of transposable elements in Alzheimer’s disease pathogenesis
Вавиловский журнал генетики и селекции
alzheimer’s disease
carcinogenesis
mirna
aging
transposons
retroelements
title Involvement of transposable elements in Alzheimer’s disease pathogenesis
title_full Involvement of transposable elements in Alzheimer’s disease pathogenesis
title_fullStr Involvement of transposable elements in Alzheimer’s disease pathogenesis
title_full_unstemmed Involvement of transposable elements in Alzheimer’s disease pathogenesis
title_short Involvement of transposable elements in Alzheimer’s disease pathogenesis
title_sort involvement of transposable elements in alzheimer s disease pathogenesis
topic alzheimer’s disease
carcinogenesis
mirna
aging
transposons
retroelements
url https://vavilov.elpub.ru/jour/article/view/4093
work_keys_str_mv AT rnmustafin involvementoftransposableelementsinalzheimersdiseasepathogenesis
AT ekkhusnutdinova involvementoftransposableelementsinalzheimersdiseasepathogenesis