[Prospects for retroelement-targeted therapy of schizophrenia]

Schizophrenia is a complex disorder with a heritability estimated at 73-79%. It is associated with numerous single-nucleotide polymorphisms (SNPs), predominantly situated in intergenic, intronic, and regulatory genomic regions. These regions harbor the majority of retroelements, and the activity and function of these elements may be influenced by the presence of specific SNPs. A review of the scientific literature revealed reliable data on the activation of the HERV, LINE, and Alu retroelements in peripheral blood, brain tissue, and cerebrospinal fluid samples from schizophrenia patients. These retroelements contribute to disorders through insertional mutagenesis, as new insertions disrupt the expression of brain-specific genes. Protein products of retroelements contribute to immune-inflammatory reactions with upregulation of C-reactive protein, caspase-1, TLR3, IL-1β, IL-2, IL-6, IL-10, TNF-α, IFN-γ, IFN-β, abnormal expression of BDNF, dopamine receptors, ASTC-1/2, GABA1, and 5-HT. Since the activation of retroelements is caused by epigenetic dysregulation, targeted therapy of schizophrenia using specific microRNAs is promising. It is proposed to use antibodies targeting HERV proteins, which have shown efficacy in multiple sclerosis, driven by abnormal HERV activation in the brain. Reverse transcriptase inhibitors can be used to reduce the transposition activity of retroelements.