Effect of amyloid-ß on the redox system activity in SH-SY5Y cells preincubated with lipopolysaccharide or co-cultured with microglia cells.

ABSTRACT

Amyloid deposits and hyperphosphorylation of the tau protein are still believed to be the two main causes of Alzheimer's disease. However, newer studies show the beneficial (including antiradical and antimicrobial) effects of amyloid at physiological concentrations. Therefore, this study aimed to investigate the impact of three amyloid fragments - 25-35, 1-40, and 1-42 at concentrations close to physiological levels on the oxidative stress induced by the administration of lipopolysaccharide (LPS) or co-culturing with microglia cells. Differentiated SH-SY5Y cells were used, constituting a model of neuronal cells that were preincubated with LPS or supernatant collected from THP-1 cell culture. The cells were treated with amyloid-ß fragments at concentrations of 0.001, 0.1, and 1.0 µM, and then biological assays were carried out. The results of the study support the antioxidant properties of Aß, which may protect neurons from the damaging effects of neuroinflammation. All tested amyloid-ß fragments reduced oxidative stress and increased the levels of enzymatic stress parameters - the activity of SOD, GPx and catalase. In addition, the administration of amyloid-ß at low physiological concentrations also increased reduced glutathione (GSH) levels and the ratio between reduced and oxidized glutathione (GSH/GSSG), which is considered a good indicator of maintaining cellular redox balance. Furthermore, a stronger antioxidant effect of 1-40 fragment was observed, occurring in a wider range of concentrations, compared to the other tested fragments 25-35 and 1-42.