Multitarget strategies in Alzheimer's disease: benefits and challenges on the road to therapeutics

Future Med Chem. 2016 Apr;8(6):697-711. doi: 10.4155/fmc-2016-0003. Epub 2016 Apr 15.

Abstract

Alzheimer's disease is a multifactorial syndrome, for which effective cures are urgently needed. Seeking for enhanced therapeutic efficacy, multitarget drugs have been increasingly sought after over the last decades. They offer the attractive prospect of tackling intricate network effects, but with the benefits of a single-molecule therapy. Herein, we highlight relevant progress in the field, focusing on acetylcholinesterase inhibition and amyloid pathways as two pivotal features in multitarget design strategies. We also discuss the intertwined relationship between selected molecular targets and give a brief glimpse into the power of multitarget agents as pharmacological probes of Alzheimer's disease molecular mechanisms.

Keywords: AChE inhibitors; Alzheimer's disease; acetylcholinesterase; amyloid-β; multitarget drugs; polypharmacology.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use*
  • Donepezil
  • Drug Discovery
  • Galantamine / chemistry
  • Galantamine / pharmacology
  • Galantamine / therapeutic use
  • Humans
  • Indans / chemistry
  • Indans / pharmacology
  • Indans / therapeutic use
  • Molecular Targeted Therapy
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Rivastigmine / chemistry
  • Rivastigmine / pharmacology
  • Rivastigmine / therapeutic use
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Galantamine
  • Donepezil
  • Rivastigmine