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

Amyloid beta-peptide (A beta) misfolding aggregates with beta-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 beta and inhibiting ROS simultaneous has become an important method for anti-AD. Herein, a nanoscale manganese-substituted polyphosphomolybdate (H(2)en)(3)[Mn(H2O)(4)][Mn(H2O)(3)](2)[P2Mo5O23](2)center dot 14.5H(2)O (abbreviated as MnPM) (en = ethanediamine) was designed and synthesized by single crystal to single crystal transformation method. MnPM can modulate the beta-sheet rich conformation of A beta aggregates, and thus reduce the formation of toxic species. Moreover, MnPM also possesses the ability to eliminate the free radicals produced by Cu2+-A beta aggregates. It can inhibit the cytotoxicity of beta-sheet-rich species and protect synapses of PC12 cells. MnPM combines the conformation modulating ability of A beta 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.

Automated summary

A nanoscale manganese-substituted polyphosphomolybdate (MnPM) was synthesized to modulate the β-sheet rich conformation of A beta aggregates, reduce the formation of toxic species, and eliminate free radicals produced by Cu2+-A beta aggregates. MnPM demonstrated the ability to inhibit cytotoxicity and protect synapses.