Natural compounds against Alzheimer's disease: molecular recognition of A?1-42 peptide by Salvia sclareoides extract and its major component, rosmarinic acid, as investigated by NMR.
Related Articles Natural compounds against Alzheimer's disease: molecular recognition of A?1-42 peptide by Salvia sclareoides extract and its major component, rosmarinic acid, as investigated by NMR.
Chem Asian J. 2013 Mar;8(3):596-602
Authors: Airoldi C, Sironi E, Dias C, Marcelo F, Martins A, Rauter AP, Nicotra F, Jimenez-Barbero J
Abstract
Amyloid peptides, A?1-40 and A?1-42, represent major molecular targets to develop potential drugs and diagnostic tools for Alzheimer's Disease (AD). In fact, oligomeric and fibrillar aggregates generated by these peptides are amongst the principal components of amyloid plaques found post mortem in patients suffering from AD. Rosmarinic acid has been demonstrated to be effective in preventing the aggregation of amyloid peptides in vitro and to delay the progression of the disease in animal models. Nevertheless, no information is available about its molecular mechanism of action. Herein, we report the NMR characterization of the interaction of Salvia sclareoides extract and that of its major component, rosmarinic acid, with A?1-42 peptide, whose oligomers have been described as the most toxic A? species in vivo. Our data shed light on the structural determinants of rosmarinic acid-A?1-42 oligomers interaction, thus allowing the elucidation of its mechanism of action. They also provide important information for the rational design of new compounds with higher affinity for A? peptides to generate new anti-amyloidogenic molecules and/or molecular tools for the specific targeting of amyloid aggregates in vivo. In addition, we identified methyl caffeate, another natural compound present in different plants and human diet, as a good ligand of A?1-42 oligomers, which also shows anti-amyloidogenic activity. Finally, we demonstrated the possibility to exploit STD-NMR and trNOESY experiments to screen extracts from natural sources for the presence of A? peptide ligands.
PMID: 23303581 [PubMed - indexed for MEDLINE]
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