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

Simioni, Elena and Bartolini, Manuela and Abu, Izuddin Fahmy and Blockley, Alix and Gotti, Cecilia and Bottegoni, Giovanni and Caporaso, Roberta and Bergamini, Christian and Andrisano, Vincenza and Cavalli, Andrea and 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

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

Item Type: Article
Keywords: Alzheimer’s disease, Nicotinic receptors, Acetylcholinesterase inhibitors, Multitarget compounds, Amyloid aggregation.
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.4155/fmc-2017-0039
Depositing User: Mellor, Ian
Date Deposited: 18 Sep 2017 09:29
Last Modified: 13 Oct 2017 05:17
URI: http://eprints.nottingham.ac.uk/id/eprint/46445

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