Multitarget drug design strategy in Alzheimer's disease: focus on cholinergic transmission and amyloid-beta aggregation
| Autor: | Alix Blockley, Roberta Caporaso, Elena Simoni, Michela Rosini, Manuela Bartolini, Christian Bergamini, Vincenza Andrisano, Anna Minarini, Giovanni Bottegoni, Ian R. Mellor, Cecilia Gotti, Andrea Cavalli, Izuddin Fahmy Abu |
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| Přispěvatelé: | Simoni, Elena, Bartolini, Manuela, Abu, Izuddin F, Blockley, Alix, Gotti, Cecilia, Bottegoni, Giovanni, Caporaso, Roberta, Bergamini, Christian, Andrisano, Vincenza, Cavalli, Andrea, Mellor, Ian R, Minarini, Anna, Rosini, Michela |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular amyloid aggregation Amyloid beta-Peptide Amyloid Protein aggregation Biology Pharmacology 01 natural sciences Neuroprotection Synaptic Transmission Protein Aggregates 03 medical and health sciences chemistry.chemical_compound multitarget compound Alzheimer Disease Drug Discovery medicine Humans Cholinesterase Inhibitor Cholinesterase Amyloid beta-Peptides Molecular Structure 010405 organic chemistry Drug Discovery3003 Pharmaceutical Science Alzheimer's disease medicine.disease Acetylcholinesterase 0104 chemical sciences 030104 developmental biology Nicotinic agonist chemistry Drug Design biology.protein Cholinergic Molecular Medicine Protein Aggregate Cholinesterase Inhibitors nicotinic receptor Neuroscience acetylcholinesterase inhibitor Human |
| Popis: | Aim: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network. Methods: By exploiting the multitarget approach, hybrid compounds have been synthesized and studied in vitro and in silico toward selected targets of the cholinergic and amyloidogenic pathways. Results: The new molecules were able to target the cholinergic system, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit amyloid-β aggregation. Conclusion: The compounds emerged as a suitable starting point for a further optimization process. |
| Databáze: | OpenAIRE |
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