The role of urokinase, T-cadherin and adiponetin in the development of endogenous depressive disorders

Abstract

Introduction The prevalence of depression averages approximately 6 % of the total population. The heritability of depression ranges from 28 % to 44 %. Genetic predisposition may be due to polymorphisms of genes involved in the processes of functioning and morphogenesis of the brain: the balance of monoamines, the action of navigational molecules and their receptors.Purpose of the study To determine the role of genes that regulate the processes of nerve cell migration and directed growth of nerve fibers of navigation receptors (PLAUR and CDH13) or their ligands (PLAU, PLAT, ADIPOQ) in the development of endogenous depression and schizophrenia in the Russian population.Materials and methods At the first stage of the study, the scientific literature was searched in the MEDLINE database. The primary prevalence of genomic variants will be established using whole genome sequencing of 20 patients with severe forms of schizophrenia and endogenous depression. Further, at least 100 patients in each group and 100 healthy donors will take part in the study.Results and discussion The urokinase receptor (uPAR) is involved in neurogenesis by regulating the trajectory of axonal growth. The level of suPAR in blood plasma can act as a biomarker of mild inflammation underlying the etiology of depression. The level of suPAR in plasma can be considered a predictor of the effectiveness of combination therapy with antidepressants and anti-inflammatory drugs. Molecules of the cadherin superfamily are involved in the development of the nervous system, the transmission of intercellular signals, and the regulation of neuronal plasticity. Polymorphisms of the CDH7, CDH9, CDH13, CDH17 genes demonstrate a correlation with the presence of depression. Adiponectin is a hormone secreted by adipose tissue. One of the adiponectin receptors, AdipoR2, stimulates neuronal plasticity and inhibits inflammation and oxidative stress. Plasma concentrations of adiponectin are reduced in depressed patients.Conclusion The results accumulated by researchers testify in favor of the important role of uPAR and T-cadherin in the processes of brain development, and most importantly, in the pathogenesis of the development of endogenous depressions.