Description | Acetylcholinesterase (AChE) is a 57 kDa protein. AChE can be monomeric (AChE-R), dimeric (AChE-E) or tetrameric (AChE-S). Tetrameric AChE-S can further interact with collagen Q (ColQ), enabling anchorage to neuromuscular junctions (NMJs), and a proline-rich membrane anchor protein (PRiMA) is responsible for the synaptic docking of AChE-S in the brain. AChE-R is a soluble monomer with a unique naturally unfolded C-terminal peptide. Because AChE-E and AChE-R are incapable of anchorage to the NMJ or to synaptic membranes through ColQ or PRiMA, only the AChE-S form of the enzyme is regarded as truly "synaptic" (Massoulié et al., 1993; Taylor et al., 1993; Silman and Sussman, 2008). |
Expression | Functional heterogeneity in AChE activity is regulated at the transcriptional, post-transcriptional and post-translational levels, leading to complex expression patterns that reflect tissue and cell-type specificity, differentiation state, physiological condition and response to external stimuli. Recent studies have also looked at regulation of AChE expression by microRNA (Hanin and Soreq, 2011). |
Localisation | Intracellular, extracellular, plasma, cerebrospinal fluid. |
Function | Acetylcholinesterase is a type B hydrolase that rapidly and selectively hydrolyzes the neurotransmitter acetylcholine (ACh) at cholinergic synapses, as well as at neuromuscular junctions (Soreq and Seidman, 2001). In addition to its catalytic function of the hydrolysis of acetylcholine, AChE has been shown to be involved in many non-cholinergic functions, such as cell growth, stem cell differentiation (Sperling et al., 2008; Falugi and Aluigi, 2012), neuritogenesis, cell adhesion (Paraoanu and Layer, 2008), synaptogenesis, activation of dopaminergic neurons, tumorigenesis, amyloid fibril assembly (Inestrosa et al., 1996; Alvarez et al., 1997), haematopoiesis and thrombopoiesis (Greenfield, 1996; Layer, 1996; Small et al., 1996). The role of acetylcholinesterase in modulating the regulation of cholinergic function is still being investigated (Shaked et al., 2009; Schliebs and Arendt, 2011). The role of AChE inhibitors in many neurodegenerative and neurodevelopmental pathologies is also being studied (Hargreaves, 2012; Li et al., 2012). |
Homology | AChE is widely conserved in the animal kingdom and is found in mammals, Drosophila, C. elegans and Torpedo californica, among others. |
Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils. |
Alvarez A, Opazo C, Alarcon R, Garrido J, Inestrosa NC. |
J Mol Biol. 1997 Sep 26;272(3):348-61. |
PMID 9325095 |
|
Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. |
Bernardi CC, Ribeiro Ede S, Cavalli IJ, Chautard-Freire-Maia EA, Souza RL. |
Cancer Genet Cytogenet. 2010 Mar;197(2):158-65. |
PMID 20193849 |
|
Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology. |
Berson A, Knobloch M, Hanan M, Diamant S, Sharoni M, Schuppli D, Geyer BC, Ravid R, Mor TS, Nitsch RM, Soreq H. |
Brain. 2008 Jan;131(Pt 1):109-19. Epub 2007 Dec 3. |
PMID 18056160 |
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Cholinesterase inhibitors for Alzheimer's disease. |
Birks J. |
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. (REVIEW) |
PMID 16437532 |
|
Early appearance and possible functions of non-neuromuscular cholinesterase activities. |
Falugi C, Aluigi MG. |
Front Mol Neurosci. 2012;5:54. Epub 2012 Apr 20. |
PMID 22529777 |
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Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease. |
Greenfield S. |
Neurochem Int. 1996 May-Jun;28(5-6):485-90. (REVIEW) |
PMID 8792328 |
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Cholinesterase-Targeting microRNAs Identified in silico Affect Specific Biological Processes. |
Hanin G, Soreq H. |
Front Mol Neurosci. 2011;4:28. Epub 2011 Oct 5. |
PMID 22007158 |
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Neurodegenerations induced by organophosphorous compounds. |
Hargreaves AJ. |
Adv Exp Med Biol. 2012;724:189-204. (REVIEW) |
PMID 22411244 |
|
Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. |
Inestrosa NC, Alvarez A, Perez CA, Moreno RD, Vicente M, Linker C, Casanueva OI, Soto C, Garrido J. |
Neuron. 1996 Apr;16(4):881-91. |
PMID 8608006 |
|
Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease. |
Layer PG. |
Neurochem Int. 1996 May-Jun;28(5-6):491-5. (REVIEW) |
PMID 8792329 |
|
Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes. |
Li AA, Lowe KA, McIntosh LJ, Mink PJ. |
J Toxicol Environ Health B Crit Rev. 2012;15(2):109-84. (REVIEW) |
PMID 22401178 |
|
Structure and functions of acetylcholinesterase and butyrylcholinesterase. |
Massoulie J, Sussman J, Bon S, Silman I. |
Prog Brain Res. 1993;98:139-46. (REVIEW) |
PMID 8248501 |
|
Virtues and woes of AChE alternative splicing in stress-related neuropathologies. |
Meshorer E, Soreq H. |
Trends Neurosci. 2006 Apr;29(4):216-24. Epub 2006 Mar 3. (REVIEW) |
PMID 16516310 |
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The role of nicotinic acetylcholine receptors in Alzheimer's disease. |
Oddo S, LaFerla FM. |
J Physiol Paris. 2006 Mar-May;99(2-3):172-9. Epub 2006 Jan 30. (REVIEW) |
PMID 16448808 |
|
Acetylcholinesterase in cell adhesion, neurite growth and network formation. |
Paraoanu LE, Layer PG. |
FEBS J. 2008 Feb;275(4):618-24. Epub 2008 Jan 17. (REVIEW) |
PMID 18205832 |
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Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia. |
Perry C, Pick M, Podoly E, Gilboa-Geffen A, Zimmerman G, Sklan EH, Ben-Shaul Y, Diamant S, Soreq H. |
Leukemia. 2007 Jul;21(7):1472-80. Epub 2007 May 3. |
PMID 17476278 |
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CREB regulates AChE-R-induced proliferation of human glioblastoma cells. |
Perry C, Sklan EH, Soreq H. |
Neoplasia. 2004 May-Jun;6(3):279-86. |
PMID 15153340 |
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The cholinergic system in aging and neuronal degeneration. |
Schliebs R, Arendt T. |
Behav Brain Res. 2011 Aug 10;221(2):555-63. Epub 2010 Dec 9. (REVIEW) |
PMID 21145918 |
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MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. |
Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, Soreq H. |
Immunity. 2009 Dec 18;31(6):965-73. Epub 2009 Dec 10. |
PMID 20005135 |
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Cholinesterase inhibition: is there evidence for disease-modifying effects? |
Shanks M, Kivipelto M, Bullock R, Lane R. |
Curr Med Res Opin. 2009 Oct;25(10):2439-46. (REVIEW) |
PMID 19678754 |
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Acetylcholinesterase: how is structure related to function? |
Silman I, Sussman JL. |
Chem Biol Interact. 2008 Sep 25;175(1-3):3-10. Epub 2008 Jun 6. (REVIEW) |
PMID 18586019 |
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Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease. |
Small DH, Michaelson S, Sberna G. |
Neurochem Int. 1996 May-Jun;28(5-6):453-83. (REVIEW) |
PMID 8792327 |
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Acetylcholinesterase--new roles for an old actor. |
Soreq H, Seidman S. |
Nat Rev Neurosci. 2001 Apr;2(4):294-302. (REVIEW) |
PMID 11283752 |
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Characterisation of cholinesterase expression during murine embryonic stem cell differentiation. |
Sperling LE, Steinert G, Boutter J, Landgraf D, Hescheler J, Pollet D, Layer PG. |
Chem Biol Interact. 2008 Sep 25;175(1-3):156-60. Epub 2008 Jun 6. |
PMID 18588865 |
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Deletion of the acetylcholinesterase locus at 7q22 associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). |
Stephenson J, Czepulkowski B, Hirst W, Mufti GJ. |
Leuk Res. 1996 Mar;20(3):235-41. |
PMID 8637218 |
|
Structure and regulation of expression of the acetylcholinesterase gene. |
Taylor P, Li Y, Camp S, Rachinsky TL, Ekstrom T, Getman D, Fuentes ME, Vellom DC, Radic Z. |
Chem Biol Interact. 1993 Jun;87(1-3):199-207. (REVIEW) |
PMID 8343976 |
|
Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas. |
Zakut H, Ehrlich G, Ayalon A, Prody CA, Malinger G, Seidman S, Ginzberg D, Kehlenbach R, Soreq H. |
J Clin Invest. 1990 Sep;86(3):900-8. |
PMID 2394839 |
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