Pharmacogenomics and proteomics of serotonergic and catcholaminergic system
Serotonergic and catecholaminergic (dopaminergic, noradrenergic) neurotransmitter systems regulate physiological functions and are also connected to the etiology of complex and polygenic neuropsychiatric disorders (Alzheimer’s disease /AD/, frontotemporal dementia, schizophrenia and depression). Etiology and psychobiological mechanisms of neuropsychiatric disorders is not well understood, but could be the result of interaction of genetic factors, specific proteins and environment.The aims of the project are;
-Determine the peripheral biochemical markers of the serotonergic (platelet serotonin, monoamine oxidase /MAO/ activity) and catecholaminergic system (dopamine-beta hydroxylase /DBH/ activity) as well as concentration of serum lipids in AD, schizophrenia and depression.
- Investigate gene polymorphisms coding for proteins involved in catecholamine synthesis (tyrosine hydroxylase, DBH, phenylethanolamine N-methyltransferase), serotonin synthesis (tryptophan hydroxylase), active neurotransmitter uptake (catecholamine and serotonin transporter), neurotransmitter degradation (MAO-A, MAO-B, catecholamine-O-methyltransferase /COMT/), catecholamine and serotonin receptors and proteins involved in cell membrane signaling pathways;
- Determine the protein expression in platelets of patients with neuropsychiatric disorders and healthy individuals;
- Investigate the relationship between the biochemical and genetic markers and treatment response.
We expect that the results of our research will contribute to a better understanding of the role of the serotonergic and catecholaminergic systems in the neurobiochemical and genetical basis of etiopathogenesis and treatment of neuropsychiatric disorders.
Peripheral biochemical markers in the blood of healthy subjects and patients with neuropsychiatric disorders will be determined using fluorimetric and photometric methods. Pharmacogenetic studies will employ molecular biology techniques (PCR, real-time PCR and RFLP), and proteomics methods for protein expression evaluation (two-dimensional gel electrophoresis coupled with mass spectrometry).
The present research is of special relevance because of the possible clinical application of the genetic and biochemical markers in the diagnosis and individualization of treatment in neuropsychiatric patients.