Organoplatinum-Substituted Polyoxometalate Inhibits β-amyloid Aggregation for Alzheimer's Therapy.

Aggregated β-amyloid (Aβ) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aβ aggregation has been broadly recognized as an efficient therapeutic strategy for curing AD. Herein, we designed and prepared an organic platinum-substituted polyoxometalate, (Me N) [PW O (SiC H NH ) PtCl ] (abbreviated as Pt -PW ) for inhibiting Aβ aggregation. The mechanism of inhibition on Aβ aggregation by Pt -PW was attributed to the multiple interactions of Pt -PW with Aβ including coordination interaction of Pt in Pt -PW with amino group in Aβ , electrostatic attraction, hydrogen bonding and van der Waals force. In cell-based assay, Pt -PW displayed remarkable neuroprotective effect for Aβ aggregation-induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μm. More importantly, the Pt -PW greatly reduced Aβ deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.