Search

One of the mechanisms for the development of autoimmune diseases is changes in epigenetic regulation, the root causes of which have not yet been established. At the same time, data on the role of transposons as sources of long noncoding ribonucleic acids (RNA) and microRNAs involved in the development of immune pathology have been accumulated. In evolution, transposable elements have become the basis for the emergence of V(D)J recombination and regulation of HLA genes. Pathological transposon activation has been revealed in type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, AicardiGoutieres and Sjgrens syndromes. The influence of exogenous viruses on the development of autoimmune diseases may be due to their interactions with transposons. Transposable elements themselves are able to activate the antiviral immune response, stimulating the hyperproduction of interferon. An assumption about changes in the activation of transposons as drivers of autoimmune pathology was made, which is reflected in the expression of non-coding RNAs, which are key epigenetic factors. The analysis of the transposon-derived microRNA database (MDTE DB) made it possible to identify 13 microRNAs associated with autoimmune diseases: systemic scleroderma (miR-31, miR-609, miR-3162), juvenile rheumatoid arthritis (miR-151), systemic lupus erythematosus (miR-198, miR-342), psoriasis (miR-224, miR-378) and myasthenia gravis (miR-421, miR-551a, miR-612, miR-891b), multiple sclerosis (miR-584 ), which serves as a proof of the proposed hypothesis. Since changes in epigenetic factors under the influence of transposons are reversible and are reflected in the expression of certain non-coding RNAs, targeted therapy using microRNAs and their analogues as tools is a promising direction in the development of specific treatment for autoimmune diseases.

Recently, a lot of data has been gathered which demonstrates neurogenesis in the brain of adult humans. In genetics, findings have been obtained that not only prove, but also elucidate the molecular mechanisms of neurogenesis. In some publications, however, morphology disputes neuronal renewal in adulthood. Therefore, this review presents the modern achievements of epigenetics, morphology, and physiology, which confirm and characterize postnatal neurogenesis in detail. We suggest that the introduction of molecular genetic technologies into morphological studies will be the starting point for the integration of these areas, complementing each other for the introduction of targeted therapy in clinical practice. Numerous evidence has been obtained of the presence of postnatal neurogenesis in adult humans in studies using bromodeoxyuridine, a carbon isotope of 14C, and 3H-thymidine, in comparative analyses of experimental data from animals. Neuronal stem cells, represented by radial glia present in the subventricular and subgranular zones of the human brain, are morphologically similar to neuroepithelial cells. They express marker proteins for astrocytes, which suggests that the proliferation of neuroglia found in adults can also indicate the regeneration of neurons. To prove this, further studies are required, with the exact identification of newly-formed cells, using specific molecular markers, and data from modern epigenetics. The integration of molecular genetic methods into morphology will facilitate not only the accurate determination of the classification of cells to a specific subpopulation but also to study the effects of various agents on the proliferation of neurons in the adult brain.

Retroelements play a key role in brain functioning in humans and other animals, since they represent dynamic regulatory elements controlling the expression of specific neuron types. The activity of retroelements in the brain is impaired under the influence of SARS-CoV-2, penetrating the blood-brain barrier. We propose a new concept, according to which the neurological complications of COVID-19 and their long-term effects are caused by modified expression of retroelements in neurons due to viral effect. This effect is implemented in several ways: a direct effect of the virus on the promoter regions of retroelement-encoding genes, virus interaction with miRNAs causing silencing of transposons, and an effect of the viral RNA on the products of retroelement transcription. Aging-related physiological activation of retroelements in the elderly is responsible for more severe course of COVID-19. The associations of multiple sclerosis, Parkinson’s disease, Guillain-Barré syndrome, acute disseminated encephalomyelitis with coronavirus lesions also indicate the role of retroelements in such complications, because retroelements are involved in the mechanisms of the development of these diseases. According to meta-analyses, COVID-19-caused neurological complications ranged 36.4-73%. The neuropsychiatric consequences of COVID-19 are observed in patients over a long period after recovery, and their prevalence may exceed those during the acute phase of the disease. Even 12 months after recovery, unmotivated fatigue, headache, mental disorders, and neurocognitive impairment were observed in 82%, 60%, 26.2-45%, and 16.2-46.8% of patients, correspondingly. These manifestations are explained by the role of retroelements in the integration of SARS-CoV-2 into the human genome using their reverse transcriptase and endonuclease, which results in a long-term viral persistence. The research on the role of specific retroelements in these changes can become the basis for developing targeted therapy for neurological consequences of COVID-19 using miRNAs, since epigenetic changes in the functioning of the genome in neurons, affected by transposons, are reversible.