[Influence of retroelements on the relationship between aging and neurodegenerative diseases.]

Abstract

During physiological aging, pathological activation of retroelements with accumulation and aggregation of beta-amyloid, tau, alpha-synuclein, and TDP-43 proteins is observed in the brain, which may be the cause of progressive decline in cognitive abilities with age. In neurodegenerative diseases, these processes are enhanced by hereditary predisposition (disease-associated polymorphisms are localized mainly in intronic and intergenic regions where retroelements are located) and specific viral infections. This leads to hyperactivation of retroelements, which is reflected in changes in epigenetic factors involved in the pathogenesis of neurodegenerative diseases, since the same viruses that cause activation and aggregation of beta-amyloid, tau, alpha-synuclein and TDP-43 stimulate transcription of retroelements. The resulting aggregates cause derepression of retroelements, since these proteins normally inhibit transcription of retroelements. The listed processes occur at the epigenetic level, since they do not affect DNA sequences, and the key participants are retroelements, which are drivers of epigenetic regulation. Therefore, for the treatment of neurodegenerative diseases, it may be promising to develop therapeutic interventions aimed at the activity of retroelements, which has already shown its effectiveness in the treatment of multiple sclerosis, an autoimmune disease of the central nervous system, in which persistent inflammation and demyelination processes lead to the onset of neurodegeneration with proven involvement of retroelements in the pathogenesis.