Endogenous retroelement expression in the gut microenvironment of people living with HIV-1
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Relationship of Retroelements with Antiviral Proteins and Epigenetic Factors in Alzheimer's Disease
Genetic factors such as allelic variants of the PSEN1, PSEN2, APP, and APOE genes play an important role in Alzheimer's disease development. Still, they cannot explain all cases of the disease and cannot form the basis for effective treatment methods for the pathology. Alzheimer's disease is the most common neurodegenerative disease, so identifying new mechanisms of pathogenesis may reveal new ways of treating it. Since Alzheimer's disease is associated with aging, the hypothesis is proposed that an important trigger mechanism for it is the pathological activation of retroelements during aging, leading to epigenetic changes. This is due to the role of retroelements in gene expression regulation and the origin of long noncoding RNAs and microRNAs from transposons, changes in the expression of which are observed both during aging and Alzheimer's disease. Normally, activation of retroelements is observed in hippocampal neuronal stem cells, which is necessary for epigenetic programming during neuronal differentiation. Direct changes in the expression of retroelements in Alzheimer's disease have also been described. It has been suggested that aging is a trigger for the development of Alzheimer's disease due to the pathological activation of retroelements. To confirm this hypothesis, an analysis of specific microRNAs associated with Alzheimer's disease and aging in the MDTE DB (microRNAs derived from Transposable elements) database was conducted. As a result, identified expression changes in Alzheimer's disease of 37 individual microRNAs derived from retroelements (25 from LINE, 7 from SINE, 5 from HERV), of which 12 changes expression during physiological aging, which confirms my hypothesis that the activation of retroelements during physiological aging is a driver for Alzheimer's disease. This is evidenced by the defeat of diseases mainly by the elderly and older adults. Since 3 of the 12 miRNAs associated with aging and Alzheimer's disease originated from SINE/MIRs that evolved from tRNAs, the role of tRNAs and the tRFs and tRNA halves derived from them in the development of Alzheimer's disease, which are evolutionarily closely related to retroelements was described. These results are promising for targeted disease therapy in the mechanisms of RNA-directed DNA methylation with possible complex use of retroelement enzyme inhibitors. Additional evidence for the role of retroelements in the development of Alzheimer's disease is that overexpression of tau, which has antiviral properties, with its interaction with beta-amyloid leads to dysregulation of retroelements, and in tauopathies, activation of ERV is determined. At the same time, the effect of retroelements as inducers of proteinopathy and tau aggregation has been described. In addition, HIV and herpes viruses, which affect beta-amyloid and tau protein, are also activators of retroelements. Also, polymorphisms associated with Alzheimer's disease are located mainly in intronic and intergenic regions where retroelements are located, affecting changes in their activity.
Relationship of Retroelements with Antiviral Proteins and Epigenetic Factors in Alzheimer's Disease
Genetic factors such as allelic variants of the PSEN1, PSEN2, APP, and APOE genes play an important role in Alzheimer's disease development. Still, they cannot explain all cases of the disease and cannot form the basis for effective treatment methods for the pathology. Alzheimer's disease is the most common neurodegenerative disease, so identifying new mechanisms of pathogenesis may reveal new ways of treating it. Since Alzheimer's disease is associated with aging, the hypothesis is proposed that an important trigger mechanism for it is the pathological activation of retroelements during aging, leading to epigenetic changes. This is due to the role of retroelements in gene expression regulation and the origin of long noncoding RNAs and microRNAs from transposons, changes in the expression of which are observed both during aging and Alzheimer's disease. Normally, activation of retroelements is observed in hippocampal neuronal stem cells, which is necessary for epigenetic programming during neuronal differentiation. Direct changes in the expression of retroelements in Alzheimer's disease have also been described. It has been suggested that aging is a trigger for the development of Alzheimer's disease due to the pathological activation of retroelements. To confirm this hypothesis, an analysis of specific microRNAs associated with Alzheimer's disease and aging in the MDTE DB (microRNAs derived from Transposable elements) database was conducted. As a result, identified expression changes in Alzheimer's disease of 37 individual microRNAs derived from retroelements (25 from LINE, 7 from SINE, 5 from HERV), of which 12 changes expression during physiological aging, which confirms my hypothesis that the activation of retroelements during physiological aging is a driver for Alzheimer's disease. This is evidenced by the defeat of diseases mainly by the elderly and older adults. Since 3 of the 12 miRNAs associated with aging and Alzheimer's disease originated from SINE/MIRs that evolved from tRNAs, the role of tRNAs and the tRFs and tRNA halves derived from them in the development of Alzheimer's disease, which are evolutionarily closely related to retroelements was described. These results are promising for targeted disease therapy in the mechanisms of RNA-directed DNA methylation with possible complex use of retroelement enzyme inhibitors. Additional evidence for the role of retroelements in the development of Alzheimer's disease is that overexpression of tau, which has antiviral properties, with its interaction with beta-amyloid leads to dysregulation of retroelements, and in tauopathies, activation of ERV is determined. At the same time, the effect of retroelements as inducers of proteinopathy and tau aggregation has been described. In addition, HIV and herpes viruses, which affect beta-amyloid and tau protein, are also activators of retroelements. Also, polymorphisms associated with Alzheimer's disease are located mainly in intronic and intergenic regions where retroelements are located, affecting changes in their activity.
Накопленные в научной литературе данные свидетельствуют о том, что болезнь Паркинсона иногда развивается после перенесенных инфекций, вызванных вирусами SARS-CoV-2, Западного Нила, Коксаки, Сент-Луиса, японского энцефалита В, гепатита В и С, гриппа А, ВИЧ, герпес-вирусами, флавивирусами. Нейроинвазивные вирусы Западного Нила и ВИЧ активируют экспрессию альфа-синуклеина, а вирусы гриппа А, SARS-CoV-2 и Коксаки В3 способствуют агрегации альфа-синуклеина, который обладает биофизическими характеристиками противовирусных пептидов и необходим для нейрональной экспрессии генов, стимулируемых интерфероном. Данные механизмы могут быть триггерами болезни Паркинсона, прогрессирование которой обусловлено вовлечением в процесс активированных под их влиянием ретроэлементов, стимулирующих интерфероновый ответ, экспрессию и агрегацию альфа-синуклеина в головном мозге. Идентифицировано непосредственное активирующее влияние описанных вирусных инфекций на ретроэлементы генома человека. Дополнительными факторами являются ассоциированные с болезнью Паркинсона старение и полиморфизмы, расположенные в межгенных, интронных и регуляторных областях, где локализуются последовательности транспозонов. Кроме того, определено влияние особенностей распределения ретроэлементов в геномах популяций людей на предрасположенность к болезни Паркинсона и роль транспозонов в моногенных формах заболевания. Эффектами патологически активированных при болезни Паркинсона ретроэлементов являются изменения экспрессии произошедших от них микроРНК, которые способствуют нарушению эпигенетической регуляции генов в головном мозге и прогрессированию патологии. Анализ научной литературы позволил описать снижение уровня 15 таких микроРНК, которые могут служить инструментами для таргетной терапии заболевания. Data accumulated in scientific literature indicate that Parkinson’s disease develops after infections caused by SARS-CoV-2, West Nile, Coxsackie, St. Louis viruses, Japanese encephalitis B, hepatitis B and C, influenza A, HIV, herpes viruses, flaviviruses. Neuroinvasive West Nile viruses and HIV activate expression of alpha-synuclein. Influenza A, SARS-CoV-2, and Coxsackie B3 viruses promote aggregation of alpha-synuclein, which has the biophysical characteristics of antiviral peptides and is required for neuronal interferon-stimulated gene expression. These mechanisms can be triggers of Parkinson’s disease, which progression is due to involvement of retroelements activated under their influence, stimulating the interferon response, expression and aggregation of alpha-synuclein in the brain. Direct activation of retroelements of the human genome by the described viral infections has been identified. Additional factors are aging and Parkinson’s disease-associated polymorphisms located in intergenic, intronic and regulatory regions where transposon sequences are localized. In addition, the influence of the distribution of retroelements in the genomes of human populations on susceptibility to Parkinson’s disease and the role of transposons in monogenic forms of the disease were determined. The effects of pathologically activated retroelements in Parkinson’s disease are changes in expression of microRNAs derived from them, which contribute to disruption of epigenetic regulation of genes in the brain and pathology progression. An analysis of the scientific literature made it possible to describe a decrease in the levels of 15 such microRNAs, which can serve as tools for targeted therapy of the disease.
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