Albumin–manganese dioxide nanocomposites: a potent inhibitor and ROS scavenger against Alzheimer's β-amyloid fibrillogenesis and neuroinflammation

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease pathologically caused by amyloid-β protein (Aβ) aggregation, oxidative stress, and neuroinflammation. The pathogenesis of AD is still uncertain and intricate, and helpful therapy has rarely been recorded. So, discovering amyloid modulators is deemed a promising avenue for preventing and treating AD. In this study, human serum albumin (HSA), a protein-based Aβ inhibitor, was utilized as a template to guide the synthesis of HSA-manganese dioxide nanocomposites (HMn NCs) through biomineralization. The in situ formed MnO2 in HSA endows this nano-platform with outstanding reactive oxygen species (ROS) scavenging capability, including superoxide dismutase-mimetic and catalase-mimetic activities, which could scavenge the plethora of superoxide anion radicals and hydrogen peroxide. More importantly, the HMn NCs show enhanced potency in suppressing Aβ fibrillization compared with HSA, which further alleviates Aβ-mediated SH-SY5Y neurotoxicity by scavenging excessive ROS. Moreover, it is demonstrated that HMn NCs reduce Aβ-related inflammation in BV-2 cells by lowering tumor necrosis factor-α and interleukin-6. Furthermore, transgenic C. elegans studies showed that HMn NCs could remove Aβ plaques, reduce ROS in CL2006 worms, and promote the lifespan extension of worms. Thus, HMn NCs provide a promising tactic to facilitate the application of multifunctional nanocomposites in AD treatment.