The role of urokinase, T-cadherin, and adiponectin in the develop - ment of schizophrenia, bipolar disorder, and Alzheimer’s disease (literature review)

Abstract

Genetic predisposition to mental and neurodegenerative diseases may be due to mutations or polymorphisms of genes involved in the functioning and morphogenesis of the brain: the balance of monoamines and the action of navigational molecules and their receptors. The urokinase-type plasminogen activator receptor (uPAR) is an important participant in the processes that regulate neurogenesis. In particular, uPAR regulates the growth trajectory of axons. An increase in the level of soluble urokinase-type plasminogen activator receptor (suPAR) is observed in patients with schizophrenia compared with the healthy population. On the contrary, in patients with bipolar disorder in the manic and depressive phases, as well as in patients suffering from Alzheimer's disease, uPAR levels decrease. Molecules of the cadherin superfamily are involved in the formation and development of the nervous system, the transmission of intercellular signals, and the regulation of nerve cell lasticity. Studies have shown that changes in the CDH12, CDH13, CDH18, and CDH23 genes are associated with the development of schizophrenia, while CDH7, CDH13 and CDH18 are associated with the development of bipolar disorder, and N-cadherin and CDH13 are associated with the development of Alzheimer's disease. Adiponectin is a hormone secreted by adipose tissue. One of the adiponectin receptors, AdipoR2, stimulates neuronal plasticity and inhibits inflammation and oxidative stress. Patients with schizophrenia show increased levels of adiponectin, which plays a unique pro-inflammatory role in this model. In patients with bipolar disorder, there is a decrease in adiponectin levels during the depressive phase. In patients with Alzheimer's disease, a decrease in adiponectin levels contributes to the progression of the disease and accelerates the onset of cognitive impairment. Understanding the role of navigational molecules, in particular urokinase, T-cadherin, and their ligands (adiponectin, etc.) in the processes of morphogenesis, leading to incorrect laying of the brain, will make it possible not only to predict the likelihood of developing mental disorders, but also to carry out their timely prevention, determine the most appropriate therapeutic strategy depending on the form of the disease, and to develop efective methods of etiotropic and pathogenetic therapy.

Novel missense variants in brain morphogenic genes associated with depression and schizophrenia

“…The rs6265-T (V66M) variant in the BDNF gene, for instance, reduces inducible BDNF production ( 59 ) and is associated with an elevated risk of MDD in the Mexican American population ( 7 ) and paranoid schizophrenia in the Chinese population ( 47 , 48 ). Spatiotemporal perturbations in PLAUR expression are presumed to contribute to autism spectrum disorders ( 60 , 61 ), a notion supported by animal studies ( 62 ). However, all previously described SNPs in the PLAUR gene associated with susceptibility to psychiatric disorders were located in noncoding regions ( 61 , 63 ).…”

“…Spatiotemporal perturbations in PLAUR expression are presumed to contribute to autism spectrum disorders ( 60 , 61 ), a notion supported by animal studies ( 62 ). However, all previously described SNPs in the PLAUR gene associated with susceptibility to psychiatric disorders were located in noncoding regions ( 61 , 63 ). Similarly, the CDH23 gene is known to be crucial for the formation of the inner ear hair apparatus ( 64 ) and for prepulse inhibition (PPI) in neuronal networks ( 65 , 66 ).…”