title: Donepezil: potential neuroprotective and disease-modifying effects.
abstract: BACKGROUND
  There is substantial evidence from preclinical studies that cholinesterase inhibitors affect basic processes that have been implicated in Alzheimer's disease (AD) pathogenesis, suggesting that these drugs should have both disease-modifying and neuroprotective effects in humans. The evidence seems to be strongest in relation to donepezil, which is the focus of this review.
  
  
  OBJECTIVE
  To summarize the preclinical literature regarding the effects of donepezil on cellular and molecular processes underlying AD. Second, to suggest reasons for the apparent disparity between robust preclinical effects and modest clinical effects of this drug and others in its class.
  
  
  METHODS
  Articles retrieved from PubMed searches were critically reviewed and selected for relevance to the current topic.
  
  
  CONCLUSIONS
  Donepezil has numerous cellular and molecular effects that should influence AD progression.
authors.affiliation: Research Cleo Roberts Center for Clinical Research, Sun Health Research Institute, 10515 W Santa Fe Drive, Sun City, AZ 85351, USA. Sandra.Jacobson@sunhealth.org
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Jacobson
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077265:Donepezil; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D000077265:Donepezil