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.
Multi-target Design Strategies in the Context of Alzheimer's Disease: Acetylcholinesterase Inhibition and NMDA Receptor Antagonism as the Driving Forces / Michela Rosini; Elena Simoni; Anna Minarini; Carlo Melchiorre. - In: NEUROCHEMICAL RESEARCH. - ISSN 0364-3190. - STAMPA. - 39:10(2014), pp. 1914-1923. [10.1007/s11064-014-1250-1]
Multi-target Design Strategies in the Context of Alzheimer's Disease: Acetylcholinesterase Inhibition and NMDA Receptor Antagonism as the Driving Forces
ROSINI, MICHELA;SIMONI, ELENA;MINARINI, ANNA;
2014
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.