engleski

Neuroprotective potential of flavonols against oxidative stress-mediated injury

At least partially, OS in Alzheimer´s disease has been linked to the impairment of copper homeostasis. Via the Fenton chemistry copper may trigger generation of extremely dangerous hydroxyl radicals and induce oxidative damage of cellular components. Polyphenolic phytochemicals, including flavonols, are generally appreciated as a promising and safe adjuvant treatment option in neuroprotection based on their antioxidative activities, metal-chelating properties, and ability to regulate redox-sensitive signalling pathways. Results performed in P19 neuronal cells by Dr. Jazvinšćak Jembrek indicate that the neuroprotective effects of quercetin are determined by the severity and the type of oxidative injury. In copper-induced OS, quercetin improved viability of moderately damaged neurons by preventing free radical accumulation and downstream apoptotic changes. At the molecular level, quercetin attenuated copper-induced increase of p53 upregulated modulator of apoptosis (PUMA) expression, reduced levels of nucleoside diphosphate kinase NME1 and modulated activity of ERK1/2 and PI3K/Akt signalling pathways. In severely injured neurons, quercetin acted pro- oxidatively and exacerbated harmful effects of copper. On the other hand, in hydrogen peroxide- induced OS, only beneficial effects of quercetin were observed. Effects of myricetin against copper-induced OS were studied in neuroblastoma SH-SY5Y cells. Myricetin demonstrated prooxidative effects, reduced viability, modulated expression of pro-apoptotic and anti-apoptotic proteins, and affected cell surface and nanomechanical properties of SH-SY5Y cells. The obtained results are relevant in the context of considering polyphenolic phytochemicals as a possible adjuvant therapy in neuroprotection, particularly in conditions accompanied with metal dyshomeostasis.

Oxidative stress ; Metal dyshomeostasis ; Copper ; Flavonols ; Neuroprotection

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