Organoplatinum-Substituted Polyoxometalate Inhibits ß-amyloid Aggregation for Alzheimer's Therapy.
Angew Chem Int Ed Engl
; 58(50): 18032-18039, 2019 12 09.
Article
em En
| MEDLINE
| ID: mdl-31591753
ABSTRACT
Aggregated ß-amyloid (Aß) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aß 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 PtII -PW11 ) for inhibiting Aß42 aggregation. The mechanism of inhibition on Aß42 aggregation by PtII -PW11 was attributed to the multiple interactions of PtII -PW11 with Aß42 including coordination interaction of Pt2+ in PtII -PW11 with amino group in Aß42 , electrostatic attraction, hydrogen bonding and van der Waals force. In cell-based assay, PtII -PW11 displayed remarkable neuroprotective effect for Aß42 aggregation-induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8â
µm. More importantly, the PtII -PW11 greatly reduced Aß deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
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Peptídeos beta-Amiloides
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article