Neurobiology of butyrylcholinesterase

Key Points

  • BuChE is a serine hydrolase that catalyzes the hydrolysis of choline and non-choline esters, including the neurotransmitter acetylcholine. This enzyme also displays aryl acylamidase activity and enhances the activity of proteases such as trypsin.

  • The gene that codes BuChE displays polymorphisms, resulting in several enzymes with different levels of activity, including enzymatically silent variants. Moreover, BuChE exists in several different molecular forms, including monomers and oligomers that consist of identical catalytic subunits.

  • In the human brain, BuChE is expressed in substantial populations of neurons, particularly in deep layers of the cerebral cortex, hippocampal formation, amygdala and many thalamic nuclei.

  • BuChE might be associated with cellular proliferation and neurite growth during the development of the nervous system.

  • In Alzheimer's disease, the cortical levels of BuChE are increased and its enzymatic properties and molecular forms are altered. Significant levels of BuChE are present within plaques and tangles, the pathological hallmarks of this disorder, and might participate in the formation of these lesions. So, BuChE inhibition might be of therapeutic value in Alzheimer's disease.

Abstract

Butyrylcholinesterase is a serine hydrolase related to acetylcholinesterase that catalyses the hydrolysis of esters of choline, including acetylcholine. Butyrylcholinesterase has unique enzymatic properties and is widely distributed in the nervous system, pointing to its possible involvement in neural function. Here, we summarize the biochemical properties of butyrylcholinesterase and review the evidence that this enzyme has important roles in cholinergic neurotransmission and could be involved in other nervous system functions and in neurodegenerative diseases.

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Figure 1: The active site of butyrylcholinesterase is at the bottom of a 20 Å gorge.
Figure 2: Molecular forms of butyrylcholinesterase.
Figure 3: The butyrylcholinesterase gene.
Figure 4: Butyrylcholinesterase- and acetylcholinesterase-expressing neurons in the human amygdala and hippocampal formation.
Figure 5: Butyrylcholinesterase and Alzheimer's disease.

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Acknowledgements

We would like to thank E. Martin and R. Walsh for their assistance and helpful discussions. The preparation of this review was made possible in part by an unrestricted educational grant from Novartis Pharma. Research on cholinesterases was supported by the Canadian Institutes of Health Research, The Scottish Rite Charitable Foundation of Canada, Capital District Health Authority Research Fund, Heart and Stroke Foundations of New Brunswick and Nova Scotia (S.D. and D.A.H.), and by Novartis Pharma. (C.G.).

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Correspondence to Sultan Darvesh or Changiz Geula.

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DATABASES

LocusLink

ACHE

BCHE

OMIM

Alzheimer disease

FURTHER INFORMATION

Encyclopedia of Life Sciences

Alzheimer disease

neurotransmitters

Glossary

DEMENTIA WITH LEWY BODIES

A neurodegenerative disorder clinically characterized, in part, by motor impairments, dementia, and psychiatric disturbances. Neuropathologically, it is characterized by the presence of intracytoplasmic inclusions called Lewy bodies in cortical and subcortical neurons. Clinically and neuropathologically, this disorder bears some resemblance to Alzheimer's and Parkinson's diseases.

SITE-DIRECTED MUTAGENESIS

The generation of a mutation at a predetermined position in a DNA sequence. The most common method involves the use of a chemically synthesized mutant DNA strand that can hybridize with the target molecule.

POLYMORPHISMS

The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.

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Darvesh, S., Hopkins, D. & Geula, C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 4, 131–138 (2003). https://doi.org/10.1038/nrn1035

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