Mustafin R N, Khusnutdinova E K
Bashkir State Medical University, Ufa, Russia.
Bashkir State Medical University, Ufa, Russia Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2024 Apr;28(2):228-238. doi: 10.18699/vjgb-24-27.
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.
阿尔茨海默病影响着平均5%的人群，且患病率随年龄显著增加，这表明衰老背后的相同机制可能影响这种病理状态。对这些机制的研究有望找到治疗和预防该疾病的有效方法。这些机制中可能的参与者是转座子，它们是表观遗传调控的驱动因素，因为它们在进化过程中在基因组中形成了非编码RNA基因的物种特异性分布。研究miRNA参与阿尔茨海默病发病机制具有重要意义，因为全基因组关联研究（GWAS）结果显示蛋白质编码基因（APOE4、ABCA7、BIN1、CLU、CR1、PICALM、TREM2）与该疾病有关联，这使得解释其复杂的发病机制变得困难。在阿尔茨海默病患者的不同脑区发现了许多基因的特定表达变化，这可能是由于转座子影响下的全局调控变化所致。实验和临床研究表明阿尔茨海默病中反转录元件存在病理性激活。我们根据MDTE数据库对科学文献的分析揭示了28种源自转座子的miRNA（17种来自长散在核元件（LINE），5种来自短散在核元件（SINE），4种来自人内源性逆转录病毒（HERV），2种来自DNA转座子），其表达在这种疾病中发生特异性变化（17种miRNA表达降低，11种miRNA表达增加）。28种miRNA中的13种（miR-151a、-192、-211、-28、-31、-320c、-335、-340、-378a、-511、-576、-708、-885）的表达也随衰老和癌症发展而变化，这表明可能存在共同的致病机制。这些miRNA大多数源自LINE反转录元件，其病理性激活与衰老、致癌作用和阿尔茨海默病有关，这支持了这样一种假说，即这三个过程基于转座子的原发性失调，而转座子是个体发育中基因表达表观遗传调控的驱动因素。
