A Nanoenzyme Constructed from Manganese and Strandberg-Type Phosphomolybdate with Versatility in Antioxidant and Modulating Conformation of A Protein Misfolding Aggregates In Vitro.

Amyloid -peptide (A) misfolding aggregates with -sheet structures and surplus reactive oxygen species (ROS) are both considered to be the culprit of neuronal toxicity in Alzheimer's disease (AD). Therefore, modulating the misfolding mode of A and inhibiting ROS simultaneous has become an important method for anti-AD. Herein, a nanoscale manganese-substituted polyphosphomolybdate (Hen)[Mn(HO)][Mn(HO)][PMoO]·14.5HO (abbreviated as MnPM) (en = ethanediamine) was designed and synthesized by single crystal to single crystal transformation method. MnPM can modulate the -sheet rich conformation of A aggregates, and thus reduce the formation of toxic species. Moreover, MnPM also possesses the ability to eliminate the free radicals produced by Cu-A aggregates. It can inhibit the cytotoxicity of -sheet-rich species and protect synapses of PC12 cells. MnPM combines the conformation modulating ability of A and anti-oxidation ability, which makes a promising multi-funcational molecular with a composite mechanism for the new conceptual designing in treatment of such protein-misfolding diseases.