Calycosin ameliorates advanced glycation end product-induced neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer?s disease

Growing pieces of evidence suggest that Alzheimer's disease (AD) is interlinked with Type 2 diabetes mellitus (DM), which has been described as type 3 DM. In this study, we investigate the neuronal insult attributable to advanced glycation end products (AGEs) as the models of DM-related AD to understand the effects exerted by calycosin on neurodegenerative changes both in vivo and in vitro studies and also studied the associated molecular mechanisms. The results reported herein revealed that the viability of the PC12 cells induced by AGEs increased when treated with calycosin. It was also observed that the learning and memory abilities of AGE-induced DM -related AD rats improved under these conditions. Analysis of the reported results indicates that calycosin can effectively down-regulate the activity of GSK-3 beta to result in the reversal of the process of tau hyper-phosphorylation, inhibit the expression of RAGE and BACE-1 proteins, resulting in a decrease in the production of beta-amyloid and regulate the PGC-1 alpha/TFAM signaling pathway to repair mitochondrial dysfunction. It can be inferred that calycosin can potentially exhibit important therapeutic properties that can be exploited during the treatment of AD, especially DM-related AD.

Automated summary

This study explores the effects of calycosin on neurodegenerative changes induced by advanced glycation end products (AGEs) in DM-related AD. The results suggest that calycosin can improve cell viability and enhance learning and memory abilities in DM-related AD models. The molecular mechanisms involve down-regulation of GSK-3 beta activity, inhibition of RAGE and BACE-1 protein expression, reduction in beta-amyloid production, and regulation of the PGC-1 alpha/TFAM signaling pathway to repair mitochondrial dysfunction.