Journal
NEUROCHEMICAL RESEARCH
Volume 39, Issue 10, Pages 1914-1923Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-014-1250-1
Keywords
Alzheimer's disease; Multifactorial disease; Multi-target-directed ligands; Acetylcholinesterase inhibition; NMDAR antagonism
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Funding
- University of Bologna
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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.
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