Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation

Background: 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 ma...

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Main Authors: Simioni, Elena, Bartolini, Manuela, Abu, Izuddin Fahmy, Blockley, Alix, Gotti, Cecilia, Bottegoni, Giovanni, Caporaso, Roberta, Bergamini, Christian, Andrisano, Vincenza, Cavalli, Andrea, Mellor, Ian R., Minarini, Anna
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Published: Future Science 2017
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Online Access:https://eprints.nottingham.ac.uk/46445/
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author Simioni, Elena
Bartolini, Manuela
Abu, Izuddin Fahmy
Blockley, Alix
Gotti, Cecilia
Bottegoni, Giovanni
Caporaso, Roberta
Bergamini, Christian
Andrisano, Vincenza
Cavalli, Andrea
Mellor, Ian R.
Minarini, Anna
author_facet Simioni, Elena
Bartolini, Manuela
Abu, Izuddin Fahmy
Blockley, Alix
Gotti, Cecilia
Bottegoni, Giovanni
Caporaso, Roberta
Bergamini, Christian
Andrisano, Vincenza
Cavalli, Andrea
Mellor, Ian R.
Minarini, Anna
author_sort Simioni, Elena
building Nottingham Research Data Repository
collection Online Access
description Background: 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. Results: By exploiting the multitarget approach, the present study provides new molecules able to target the cholinergic pathway, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit Aβ aggregation. Conclusions: These new compounds emerged as a suitable starting point for a further optimization process.
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spelling nottingham-464452020-05-04T18:51:04Z https://eprints.nottingham.ac.uk/46445/ Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation Simioni, Elena Bartolini, Manuela Abu, Izuddin Fahmy Blockley, Alix Gotti, Cecilia Bottegoni, Giovanni Caporaso, Roberta Bergamini, Christian Andrisano, Vincenza Cavalli, Andrea Mellor, Ian R. Minarini, Anna Background: 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. Results: By exploiting the multitarget approach, the present study provides new molecules able to target the cholinergic pathway, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit Aβ aggregation. Conclusions: These new compounds emerged as a suitable starting point for a further optimization process. Future Science 2017-06-20 Article PeerReviewed Simioni, Elena, Bartolini, Manuela, Abu, Izuddin Fahmy, Blockley, Alix, Gotti, Cecilia, Bottegoni, Giovanni, Caporaso, Roberta, Bergamini, Christian, Andrisano, Vincenza, Cavalli, Andrea, Mellor, Ian R. and Minarini, Anna (2017) Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation. Future Medicinal Chemistry, 9 (10). pp. 953-963. ISSN 1756-8927 Alzheimer’s disease Nicotinic receptors Acetylcholinesterase inhibitors Multitarget compounds Amyloid aggregation. https://www.future-science.com/doi/full/10.4155/fmc-2017-0039 10.4155/fmc-2017-0039 10.4155/fmc-2017-0039 10.4155/fmc-2017-0039
spellingShingle Alzheimer’s disease
Nicotinic receptors
Acetylcholinesterase inhibitors
Multitarget compounds
Amyloid aggregation.
Simioni, Elena
Bartolini, Manuela
Abu, Izuddin Fahmy
Blockley, Alix
Gotti, Cecilia
Bottegoni, Giovanni
Caporaso, Roberta
Bergamini, Christian
Andrisano, Vincenza
Cavalli, Andrea
Mellor, Ian R.
Minarini, Anna
Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title_full Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title_fullStr Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title_full_unstemmed Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title_short Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
title_sort multitarget drug design strategy in alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation
topic Alzheimer’s disease
Nicotinic receptors
Acetylcholinesterase inhibitors
Multitarget compounds
Amyloid aggregation.
url https://eprints.nottingham.ac.uk/46445/
https://eprints.nottingham.ac.uk/46445/
https://eprints.nottingham.ac.uk/46445/