Neuropharmacology

Biography

Biography: Michael V Ugrumov

Abstract

Motor symptoms first appear at Parkinson's disease (PD) many years after the onset of the degradation of the nigrostriatal system, at a loss of most dopaminergic (DA-ergic) neurons and depletion of neuroplasticity, which explains low efficiency of current therapy. Therefore, the development of the diagnostics of PD at the preclinical stage is of the highest priority. It is mainly based on a search for biomarkers as a change in the composition of plasma and expression of specific genes and phenotype of blood cells in untreated patients at the early clinical stage although there is no guarantee that biomarkers, found at the clinical stage are also characteristic of preclinical stage. That is why, in addition to patients, we searched for biomarkers in the blood in MPTP-treated mice at the early symptomatic stage and presymptomatic stage of parkinsonism. According to our data, the concentration of some markers in plasma, e.g., L-DOPA, were modified in the same way in PD patients and mice at both stages of parkinsonism. The concentration of others, e.g., DOPAC differed at the presymptomatic stage in mice from those in mice at the symptomatic stage and patients. Apparently the former markers are more reliable than the latter. Moreover, in experimental models, we developed a new approach to preclinical diagnosis of PD by using a pharmacological provocation test (reversible inhibitor of dopamine synthesis), which induces a short-term increase in failure of the nigrostriatal system and the appearance of motor disorders. Development of preclinical diagnostics of PD basing on the search for biomarkers in the blood in untreated PD patients and experimental models and the use of a provocative test would allow to use neuroprotective pharmacotherapy for slowing down neurodegeneration and thereby prolongation of a asymptomatic period.