Title:Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool
Volume: 21
Issue: 1
Author(s): Zhe Ying Ha, Shintu Mathew and Keng Yoon Yeong*
Affiliation:
- School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor,Malaysia
Keywords:
Butyrylcholinesterase, Alzheimer's disease, Parkinson’s disease, obesity, cocaine addiction, inflammation.
Abstract: Butyrylcholinesterase is a serine hydrolase that catalyzes the hydrolysis of esters in the
body. Unlike its sister enzyme acetylcholinesterase, butyrylcholinesterase has a broad substrate scope
and lower acetylcholine catalytic efficiency. The difference in tissue distribution and inhibitor sensitivity
also points to its involvement external to cholinergic neurotransmission. Initial studies on butyrylcholinesterase
showed that the inhibition of the enzyme led to the increment of brain acetylcholine
levels. Further gene knockout studies suggested its involvement in the regulation of amyloid-beta, a
brain pathogenic protein. Thus, it is an interesting target for neurological disorders such as Alzheimer’s
disease. The substrate scope of butyrylcholinesterase was recently found to include cocaine, as well as
ghrelin, the “hunger hormone”. These findings led to the development of recombinant butyrylcholinesterase
mutants and viral gene therapy to combat cocaine addiction, along with in-depth studies on
the significance of butyrylcholinesterase in obesity. It is observed that the pharmacological impact of
butyrylcholinesterase increased in tandem with each reported finding. Not only is the enzyme now
considered an important pharmacological target, it is also becoming an important tool to study the
biological pathways in various diseases. Here, we review and summarize the biochemical properties of
butyrylcholinesterase and its roles, as a cholinergic neurotransmitter, in various diseases, particularly
neurodegenerative disorders.