Neoagarohexaose Protects against Amyloid β-Induced Oxidative Stress and Aggregation.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Neuritic plaques containing amyloid-β protein (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein constitute major neuropathological hallmarks of AD. The neurotoxicity of aggregated Aβ has been implicated as a critical cause in the pathogenesis of AD. The aim of this study was to exam the use of neoagarohexaose (NAH) in the potential treatment of AD effects, using SH-SY5Y neuronal cell line exposed to β-amyloid protein (Aβ1-42). The present study was designed to explore the neuroprotective effects of NAH on neuroblastoma SH-SY5Y cells as a function of dosage. The cells were exposed to Aβ1-42 with or without NAH (26.7, 53.4, and 106.8 μM) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used for detecting the viability of treated cells. In treated cells, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were determined using their manufacturer kits. Flow cytometry analysis was used to assess apoptosis, changes in intracellular calcium concentration, and the mitochondrial membrane potential (MMP) after treatment. Additionally, changes in the mechanism of Aβ1-42 aggregation in the presence of NAH were explored using thioflavin T (ThT) and Congo red (CR) assays. The results showed that incubation with NAH prior to Aβ1-42 exposure increased cell survival and prevented reactive oxygen species generation. Moreover, NAH decreased the apoptotic rate, inhibited MMP depolarization, reversed the change in intracellular calcium concentration, enhanced the activities of SOD and GSH-Px, and decreased the level of MDA. In addition, the results showed that NAH, which reduced the absorption of the amyloid indicator ThT and CR dyes, was a potent inhibitor of Aβ fibrillogenesis. In conclusion, NAH protects SH-SH5Y cells from Aβ-induced damage by reducing oxidative stress and weakens the spontaneous amyloid formation of Aβ fibrils in vitro and can inhibit the amyloidization of amyloid β protein (Aβ). This study shows that NAH may be a promising anti-AD drug candidate for AD treatment. [ABSTRACT FROM AUTHOR]