An overview of the current and novel drugs for Alzheimer's disease with particular reference to anti-cholinesterase compounds.
Several cellular processes could be targeted if the complex nature of Alzheimer's disease (AD) was already understood. Most of AD treatments have been focused on the inhibition of acetylcholinesterase (AChE) in order to raise the levels of its substrate, i.e. the neurotransmitter acetylcholine (ACh), to augment cognitive functions of affected patients. Effectiveness in AChE inhibition and side-effect issues of clinical (tacrine, donepezil, galanthamine and rivastigmine) as well as of novel inhibitors is reviewed here. Novel design methods for the inhibition of AChE include the use of in silico tools to predict the interactions between AChE and the desired compound, both at the active site of the enzyme, responsible of hydrolysing ACh and with the peripheral anionic site (PAS), which has been described as a promoting agent of the amyloid beta-peptide (A beta) aggregation present in the senile plaques of the brain of AD individuals.
Colombres
Marcela
M
Centro FONDAP de Regulación Celular y Patología, Joaquín V. Luco, MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Sagal
Juan Paulo
JP
Inestrosa
Nibaldo C
NC
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000145:classification / Q000627:therapeutic use*; D006801:Humans; D018697:Nootropic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
D000682:Amyloid; D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents