Title : Butyrylcholinesterase: an important new target in Alzheimer's disease therapy - Greig_2002_Int.Psychogeriatr_14_77 |
Author(s) : Greig NH , Lahiri DK , Sambamurti K |
Ref : Int Psychogeriatr , 14 :77 , 2002 |
Abstract :
Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BCHE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BCHE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BCHE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BCHE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BCHE in AD and related dementias. Recent evidence suggests that both AChE and BCHE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BCHE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options. |
PubMedSearch : Greig_2002_Int.Psychogeriatr_14_77 |
PubMedID: 12636181 |
Inhibitor | Cymserine |
Greig NH, Lahiri DK, Sambamurti K (2002)
Butyrylcholinesterase: an important new target in Alzheimer's disease therapy
Int Psychogeriatr
14 :77
Greig NH, Lahiri DK, Sambamurti K (2002)
Int Psychogeriatr
14 :77