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.
Department of Experimental and Applied Pharmacology, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy. racchi@unipv.it
Marco
M
Racchi
Michela
M
Mazzucchelli
Emanuela
E
Porrello
Cristina
C
Lanni
Stefano
S
Govoni
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*
D016564:Amyloid beta-Protein Precursor; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents