A coordinated multi-target approach based on chondroitin sulphate nano-selenium mitigates Alzheimer's disease...

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterised by progressive memory loss and cognitive decline. Because of the lack of effective treatment modalities for AD, novel therapeutics that could delay the progression of AD are urgently required. In this study, the neuroprotective effects and mechanisms of chondroitin sulphate nano-selenium (CS@Se) were investigated by using APPSwe, PSEN1dE9 (APP/PS1) transgenic mice. We found CS@Se to exhibit potent multi-targeted anti-AD effects, and it showed excellent ability to effectively alleviate neuropathy and cognitive dysfunction. Behavioural experiments showed that CS@Se improved learning and memory capacity and enhanced motor activity. Mechanistically, CS@Se upregulated A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression while downregulating the levels of amyloid precursor protein (APP) and beta-secretase 1 (BACE1). Further studies revealed that CS@Se could reduce β-amyloid (Aβ) deposition and inhibit tau phosphorylation by promoting APP hydrolysis and inhibiting the glycogen synthase kinase (GSK)-3β signalling pathway in APP/PS1 mice. Additionally, CS@Se could alleviate oxidative stress damage, neuroinflammation, and cholinergic damage. In conclusion, CS@Se confers substantial neuroprotective effects by modulating several key pathological pathways, providing evidence for its multi-target therapeutic strategy against AD.