Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer's disease.
Proc Natl Acad Sci U S A
; 105(19): 6813-8, 2008 May 13.
Article
em En
| MEDLINE
| ID: mdl-18463291
ABSTRACT
Amelyoid-beta peptide (Abeta) is a major causative agent responsible for Alzheimer's disease (AD). Abeta contains a high affinity metal binding site that modulates peptide aggregation and toxicity. Therefore, identifying molecules targeting this site represents a valid therapeutic strategy. To test this hypothesis, a range of L-PtCl(2) (L = 1,10-phenanthroline derivatives) complexes were examined and shown to bind to Abeta, inhibit neurotoxicity and rescue Abeta-induced synaptotoxicity in mouse hippocampal slices. Coordination of the complexes to Abeta altered the chemical properties of the peptide inhibiting amyloid formation and the generation of reactive oxygen species. In comparison, the classic anticancer drug cisplatin did not affect any of the biochemical and cellular effects of Abeta. This implies that the planar aromatic 1,10-phenanthroline ligands L confer some specificity for Abeta onto the platinum complexes. The potent effect of the L-PtCl(2) complexes identifies this class of compounds as therapeutic agents for AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Peptídeos beta-Amiloides
/
Doença de Alzheimer
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2008
Tipo de documento:
Article