Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection

Eur J Med Chem. 2013:70:165-88. doi: 10.1016/j.ejmech.2013.09.050. Epub 2013 Oct 6.

Abstract

Acetylcholinesterase is a member of the α/β hydrolase protein super family, with a significant role in acetylcholine-mediated neurotransmission. Research in the modulators of AChEs has moved from a potent poison (Sarin, Soman) in war times to the potent medicine (physostigmine) in peaceful times. Natural anti-AChE includes carbamates, glycoalkaloids, anatoxins derived from green algae; synthetic anti-AChE includes highly poisonous organophosphates used as nerve gases and insecticides. Recently, the role of anti-AChE was reassessed from neurotoxins to neuron-protective in the diseases characterized by impaired acetylcholine-mediated neurotransmission like Alzheimer's disease (AD). So, the AChE has been proven to be the most viable therapeutic target for the symptomatic treatment of AD. This review article gives a spectrum of strategies to design AChE inhibitors used in the Alzheimer therapy.

Keywords: Acetylcholine; Acetylcholinesterase; Alzheimer's disease; Nerve gases.

Publication types

  • Review

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism
  • Animals
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Drug Design
  • Humans
  • Molecular Structure

Substances

  • Cholinesterase Inhibitors
  • Acetylcholinesterase