Chondroitin sulphate modified MoS 2 nanoenzyme with multifunctional activities for treatment of Alzheimer's disease

Nano-MoS exhibit oxidoreductase-like activities, and has been shown to effectively eliminate excessive intracellular ROS and inhibit Aβ aggregation, thus demonstrating promising potential for anti-Alzheimer's disease (anti-AD) intervention. However, the low water dispersibility and high toxicity of nano-MoS limits its further application. In this study, we developed a chondroitin sulphate (CS)-modified MoS nanoenzyme (CS@MoS ) by harnessing the excellent biocompatibility of CS and the exceptional activities of nano-MoS to explore its potential in anti-AD research. Promisingly, CS@MoS significantly inhibited Aβ aggregation and prevented toxic injury in SH-SY5Y cells caused by Aβ . In addition, CS@MoS protected these cells from oxidative stress damage by regulating ROS production, as well as promoting the activities of SOD and GSH-Px. CS@MoS also modulated the intracellular Ca imbalance and downregulated Tau hyperphosphorylation by activating GSK-3β. CS@MoS suppressed p-NF-κB (p65) translocation to the nucleus by inhibiting MAPK phosphorylation, and modulated the expression of downstream anti- and proinflammatory cytokines. Owing to its multifunctional activities, CS@MoS effectively improved spatial learning, memory, and anxiety in D-gal/AlCl -induced AD mice. Taken together, these results indicate that CS@MoS has significant potential for improving the therapeutic efficacy of the prevention and treatment of AD, while also presenting a novel framework for the application of nanoenzymes.