Self-assembly hollow manganese Prussian white nanocapsules attenuate Tau-related neuropathology and cognitive decline.

Abstract Alzheimer's disease (AD) is a prevalent chronic neurodegenerative disease. However, to date, none of the developed drug candidates targeting at a single therapeutic target of AD have achieved success in clinical trials. Herein, we proposed a hypothesis of hollow manganese Prussian white nanocapsules (HMPWCs)-mediated attenuation of Tau-related pathology and alleviation of cognitive decline via simultaneously alleviating neuroinflammation, scavenging reactive oxygen species, and reducing hyperphosphorylated Tau proteins. The HMPWCs self-assemblied with manganese Prussian white analogue and bovine serum albumin via a novel biomimetic mineralization present good biocompatibility, variable valence states, and low oxidation-reduction potential. They own the outstanding capabilities of relieving oxidative stress, inhibiting Tau neuropathology, and counteracting neuroinflammation, which could be used to treat Tau-related AD-like neurodegeneration. Importantly, they can also attenuate the cognitive impairments of Tau-related AD-like rats without significant side effects. This research takes the advantages of catalytic chemistry, nanomedicine and specific neurodegenerative microenvironment together, providing an alternative efficient treatment strategy for Tau-related neurodegeneration diseases, such as AD, Pick's disease, frontotemporal dementia, Creutzfeldt-Jakob Disease and progressive supranuclear palsy.