Targeting acetylcholinesterase to treat neurodegeneration.
Neurodegenerative disorders, such as Alzheimer's disease, are often characterised by the degeneration of the cholinergic system. Thus, the aim of many treatment regimens is to support this system either by means of muscarinic agonists or by inhibitors of acetylcholinesterase (AChE), the latter being able to increase the concentration of acetylcholine. However, both pharmacological groups of drugs can only help in the beginning of the progressive disease. The finding that the occupation of the peripheral anionic site of AChE is able to stop the formation of the amyloid plaque led to the development of bivalent ligands that occupy both the active and the peripheral site. This dual action might be more beneficial for treatment of Alzheimer s disease than simple inhibition of the acetylcholine hydrolysis. Thus, the new bivalent ligands are the focus of this review.
Holzgrabe
Ulrike
U
Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany. u.holzgrabe@pzlc.uni-wuerzburg.de
Kapková
Petra
P
Alptüzün
Vildan
V
Scheiber
Josef
J
Kugelmann
Eva
E
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000201:enzymology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase