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

Research output: Contribution to journalArticlepeer-review

Authors

  • Elena Simoni
  • Manuela Bartolini
  • Izuddin F. Abu
  • Alix Blockley
  • Cecilia Gotti
  • Roberta Caporaso
  • Christian Bergamini
  • Vincenza Andrisano
  • Andrea Cavalli
  • Ian R. Mellor
  • Anna Minarini
  • Michela Rosini

Colleges, School and Institutes

External organisations

  • Università di Bologna
  • University of Nottingham
  • University of Kuala Lumpur
  • Istituto per i Processi Chimico-Fisici del Consiglio Nazionale delle Ricerche (IPCF-CNR)
  • Istituto Italiano di Tecnologia

Abstract

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.

Details

Original languageEnglish
Pages (from-to)953-963
Number of pages11
JournalFuture Medicinal Chemistry
Volume9
Issue number10
Publication statusPublished - 1 Jun 2017

Keywords

  • acetylcholinesterase inhibitors, Alzheimer's disease, amyloid aggregation, multitarget compounds, nicotinic receptors