[Viral-epigenetic hypothesis of Parkinson's disease etiopathogenesis.]

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.