Chitosan oligosaccharides (COSs) have been reported to possess a broad range of activities such as antitumor, antioxidant and neuroprotective activities. In this study, the protective effects and mechanisms of peracetylated chitosan oligosaccharides (PACOs) against Aβ-induced cognitive deficits were investigated in Sprague-Dawley (SD) rats. PACOs treatment significantly improved the learning and memory function of Alzheimer's disease (AD) rats and attenuated the neuron cell damage caused by Aβ. PACOs also markedly reduced the levels of lactate dehydrogenase (LDH) and Malondialdehyde (MDA) and decreased the phosphorylation of Tau protein to inhibit oxidative injury and inflammatory responses in AD rats. Further studies indicated that PACOs may promote the repair of Aβ induced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3β signaling pathway. Consistently, the transcriptome analysis verified that the differentially expressed genes (DEGs) were mainly involved in neuron development and the PI3K-Akt signaling pathway. Taken together, peracetylated chitosan oligosaccharides (PACOs) have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3β signaling pathway.
Supplementary information: The online version contains supplementary material available at 10.1007/s42995-023-00172-3.
Keywords: Amyloid; Cognitive deficit; Neuroprotective; PI3K/Akt/GSK3β pathway; Peracetylated chitosan oligosaccharides.
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