Acetylcholinesterase inhibitors: novel activities of old molecules

The therapeutic approach for improving the cognitive function in patients with Alzheimer's disease (AD) is mainly based on the potentiation of central cholinergic activity and is achieved clinically by the use of acetylcholinesterase (AChE) inhibitors such as tacrine, donepezil, rivastigmine, galantamine and other drugs currently in clinical trials. These are, by their pharmacology, only symptomatic drugs yet recently these molecules have shown some potential also in the modulation of amyloid precursor protein (APP) processing. We explore in this review the experimental evidence that suggests a role for AChEIs in APP processing and point to multiple complex mechanisms involving either a cholinergic agonist effect, coupled to multiple signal transduction pathways, or post-transcriptional effects that modulate the expression of cellular APP. (C) 2004 Elsevier Ltd. All rights reserved.