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, (Me₄ N)₃ [PW₁₁ O₄₀ (SiC₃ H₆ NH₂ )₂ PtCl₂ ] (abbreviated as Pt^II -PW₁₁ ) for inhibiting Aβ₄₂ aggregation. The mechanism of inhibition on Aβ₄₂ aggregation by Pt^II -PW₁₁ was attributed to the multiple interactions of Pt^II -PW₁₁ with Aβ₄₂ including coordination interaction of Pt²⁺ in Pt^II -PW₁₁ with amino group in Aβ₄₂ , electrostatic attraction, hydrogen bonding and van der Waals force. In cell-based assay, Pt^II -PW₁₁ displayed remarkable neuroprotective effect for Aβ₄₂ aggregation-induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μm. More importantly, the Pt^II -PW₁₁ 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.