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

Abstract

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 A? aggregation. Conclusions: These new compounds emerged as a suitable starting point for a further optimization process.

Citation

Simioni, E., Bartolini, M., Abu, I. F., Blockley, A., Gotti, C., Bottegoni, G., …Minarini, A. (in press). Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation. Future Medicinal Chemistry, 9(10), https://doi.org/10.4155/fmc-2017-0039

• Journal Article Type: Article
• Acceptance Date: Apr 4, 2017
• Online Publication Date: Jun 20, 2017
• Deposit Date: Sep 18, 2017
• Publicly Available Date: Sep 18, 2017
• Journal: Future Medicinal Chemistry
• Print ISSN: 1756-8919
• Electronic ISSN: 1756-8927
• Publisher: Future Science
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 10
• DOI: https://doi.org/10.4155/fmc-2017-0039
• Keywords: Alzheimer’s disease, Nicotinic receptors, Acetylcholinesterase inhibitors, Multitarget compounds, Amyloid aggregation.
• Public URL: https://nottingham-repository.worktribe.com/output/867422
• Publisher URL: https://www.future-science.com/doi/full/10.4155/fmc-2017-0039