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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

Authors

Elena Simioni

Manuela Bartolini

Izuddin Fahmy Abu judd81@gmail.com

Alix Blockley

Cecilia Gotti

Giovanni Bottegoni

Roberta Caporaso

Christian Bergamini

Vincenza Andrisano

Andrea Cavalli

Ian R. Mellor ian.mellor@nottingham.ac.uk

Anna Minarini



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.

Journal Article Type Article
Journal Future Medicinal Chemistry
Print ISSN 1756-8919
Electronic ISSN 1756-8927
Publisher Future Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 10
APA6 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), doi:10.4155/fmc-2017-0039
DOI https://doi.org/10.4155/fmc-2017-0039
Keywords Alzheimer’s disease, Nicotinic receptors, Acetylcholinesterase inhibitors, Multitarget compounds, Amyloid aggregation.
Publisher URL https://www.future-science.com/doi/full/10.4155/fmc-2017-0039
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


Rosini_Manuscript_revised.pdf (883 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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