Multi-target design strategies in the context of Alzheimer's disease: acetylcholinesterase inhibition and NMDA receptor antagonism as the driving forces.
Neurochem Res
; 39(10): 1914-23, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24493627
ABSTRACT
In recent years, the multi-target-directed ligand concept has been used to design a variety of molecules hitting different biological targets for Alzheimer's disease. We have sought to combine, in the same molecule, the neuroprotective action of N-methyl-D-aspartate receptor antagonism with the symptomatic relief offered by cholinergic activity through acetylcholinesterase inhibition. This strategy could potentially maintain the positive outcomes of memantine-acetylcholinesterase inhibitor combinations, but with the benefits of a single molecule therapy. Herein, we discuss selected examples of multifunctional compounds, which we rationally designed to simultaneously modulate these targets. We also examine the intertwined relationship between acetylcholinesterase, N-methyl-D-aspartate receptors, and other active players in the neurotoxic cascade.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
/
Inibidores da Colinesterase
/
Receptores de N-Metil-D-Aspartato
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Doença de Alzheimer
Limite:
Humans
Idioma:
En
Revista:
Neurochem Res
Ano de publicação:
2014
Tipo de documento:
Article