Neuroprotekcyjne właściwości piceatannolu w modelowych układach biologicznych

Abstract

As the population is aging, the incidence of neurodegeneration diseases is increasing. Hence, the prevention and/or slowing down of neurodegeneration processes are currently one of the most important challenges the modern science is facing. Many authors demonstrated that the polyphenolic compounds, have the beneficial, pleiotropic effect in this aspect. One of such example are stilbene derivatives eg. a naturally occurring analogue of resveratrol – piceatannol. These compounds, in addition to strong antioxidant properties, inhibit cytokine secretion and regulate signaling pathways involved in the aging process. Moreover, they exhibit strong anti-amyloidogenic properties as they convert conformers formed during amyloid peptide aggregation into non-toxic products. The aim of the presented doctoral thesis was to determine the biological properties and the mechanism of action of piceatannol under oxidative stress conditions in model containing GAPDH, as well as in two cell lines. For these studies, hippocampal cell line (mHippoE-18) and neuroblastoma cell line (N2a), which represent the common in vitro models for the study of the molecular mechanisms involved in the manifestation of the neurodegenerative processes were used. The obtained results have shown that piceatannol almost completely inhibits GAPDH aggregation induced by hydrogen peroxide. It also significantly reduces nuclear translocation of GAPDH in hippocampal cells. Studies using N2a line have shown that protective effect of piceatannol is associated with an increase in both the activity and expression of glutathione peroxidases. Findings from the conducted studies allow to conclude that piceatannol has a multi-directional, neuroprotective effect. The obtained results may be the basis for further detailed investigations aimed at developing the new pro-health strategies of treatment and prevention of age-related diseases.