Butyrylcholinesterase: A Multifaceted Pharmacological Target and Tool
Autor: | Keng Yoon Yeong, Zhe Ying Ha, Shintu Mathew |
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Rok vydání: | 2020 |
Předmět: |
Pharmacology
Biology Synaptic Transmission Biochemistry Substrate Specificity Cocaine-Related Disorders 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cocaine Alzheimer Disease medicine Humans Molecular Targeted Therapy Obesity Neurotransmitter Molecular Biology Gene knockout Butyrylcholinesterase 030304 developmental biology Neurotransmitter Agents 0303 health sciences Amyloid beta-Peptides Brain Parkinson Disease Serine hydrolase Cell Biology General Medicine Acetylcholinesterase Acetylcholine Ghrelin Recombinant Proteins chemistry Cholinergic 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Current Protein & Peptide Science. 21:99-109 |
ISSN: | 1389-2037 |
Popis: | 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. |
Databáze: | OpenAIRE |
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