Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain
Open accessAbstract
Background Butyrylcholinesterase (BChE), also known as the "pseudo" or "non-neuronal" cholinesterase, is traditionally thought to have a restricted CNS distribution and to play little, if any, role in cholinergic transmission.Objective To reanalyze the role of BChE in the human brain with more sensitive methodology.Methods Three brains were examined with acetylcholinesterase and BChE histochemistry. The sections were examined with bright- and dark-field microscopy.Results The histochemical parameters used in the present experiments showed that BChE activity was present in all hippocampal and temporal neocortical areas known to receive cholinergic input. At all of these locations, the BChE enzyme could hydrolyze the acetylcholine surrogate acetylthiocholine. A substantial portion of the hippocampal and neocortical BChE appeared to be located within neuroglia and their processes.Conclusions Butyrylcholinesterase may have a greater role in cholinergic transmission than previously surmised, making BChE inhibition an important therapeutic goal in Alzheimer's disease. The results also suggest that the role of neuroglia in cholinergic transmission may be analogous to their well known role in glutamatergic transmission.
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Increasing acetylcholine concentration at the synapse by inhibiting AChE is one approach to slow down the progression of AD.
“An increase of acetylcholine concentration (ACh) at the synapse by inhibiting the acetylcholinesterase (AChE) is one of the approaches to slow down the progression of AD [18,19,20,21,22,23,24,25,26].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [25]
Cites
A "DIRECT-COLORING" THIOCHOLINE METHOD FOR CHOLINESTERASES
Karnovsky, M. J., & ROOTS, L. (1964) · Journal of Histochemistry & Cytochemistry · doi:10.1177/12.3.219 · Cited by 3,389 · see citing works
A Histochemical Method for Localizing Cholinesterase Activity.
Koelle, G. B., & Friedenwald, J. S. (1949) · Experimental Biology and Medicine · doi:10.3181/00379727-70-17013 · Cited by 1,192 · see citing works
The biology of cholinesterases
Silver, A. (1974) · Medical Entomology and Zoology · Cited by 890 · see citing works
Mesulam, M. M., Guillozet-Bongaarts, A. L., Shaw, P. L., Levey, A. I., Duysen, E. G., & Lockridge, O. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00613-3 · Cited by 654 · see citing works
Self-citationCompartmentation of Brain Glutamate Metabolism in Neurons and Glia
Daikhin, Y., & Yudkoff, M. (2000) · Journal of Nutrition · doi:10.1093/jn/130.4.1026s · Cited by 350 · see citing works
Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.
Harel, M., Sussman, J. L., Krejci, É., Bon, S., Chanal, P., Massoulié, J., & Silman, I. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10827 · Cited by 291 · see citing works
Xie, W., Stribley, J. A., Chatonnet, A., Wilder, P. J., Rizzino, A., McComb, R. D., Taylor, P., Hinrichs, S. H., & Lockridge, O. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39312-7 · Cited by 255 · see citing works
Wright, C. I., Geula, C., & Mesulam, M.-M. (1993) · Annals of Neurology · doi:10.1002/ana.410340312 · Cited by 237 · see citing works
Self-citationCortical cholinergic fibers in aging and Alzheimer's disease: A morphometric study
Geula, C., & Mesulam, M. M. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90399-0 · Cited by 202 · see citing works
Self-citationCholinesterases and Cholinesterase Inhibitors
Harrell, L. E. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.516 · Cited by 176 · see citing works
Mesulam, M. M., Geula, C., & Morán, M. A. (1987) · Annals of Neurology · doi:10.1002/ana.410220603 · Cited by 175 · see citing works
Self-citationBeach, T. G., Kuo, Y., Spiegel, K., Emmerling, M. R., Sue, L. I., Kokjohn, K., & Roher, A. E. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.4.308 · Cited by 153 · see citing works
Mesulam, M. M. (1996) · Progress in brain research · doi:10.1016/s0079-6123(08)62112-3 · Cited by 120 · see citing works
Self-citationMesulam, M., & Geula, C. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903060202 · Cited by 105 · see citing works
Self-citationElectron microscopic localization of cholinesterase activity in Alzheimer brain tissue
Carson, K. A., Geula, C., & Mesulam, M. ‐. (1991) · Brain Research · doi:10.1016/0006-8993(91)90508-s · Cited by 99 · see citing works
Self-citationMesulam, M. M., & Geula, C. (1992) · Brain Research · doi:10.1016/0006-8993(92)90543-i · Cited by 93 · see citing works
Self-citationAcetylcholinesterase: structure and use as a model for specific cation—protein interactions
Sussman, J. L., & Silman, I. (1992) · Current Opinion in Structural Biology · doi:10.1016/0959-440x(92)90207-n · Cited by 84 · see citing works
Acetylcholinesterase fiber staining in the human hippocampus and parahippocampal gyrus
Green, R. C., & Mesulam, M. M. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902730405 · Cited by 72 · see citing works
Self-citationDegradation of acetylcholine in human airways: role of butyrylcholinesterase
Norel, X., Angrisani, M., Labat, C., Gorenne, I., Dulmet, É., Rossi, F., & Brink, C. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13486.x · Cited by 55 · see citing works
Acetylcholinesterase: Structure and use as a model for specific cation-protein interactions
Sussman, J. L., & Silman, I. (1992) · Current Biology · doi:10.1016/0960-9822(92)90176-b · Cited by 44 · see citing works
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Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease.
Marucci, G., Buccioni, M., Ben, D. D., Lambertucci, C., Volpini, R., & Amenta, F. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108352 · Cited by 1,147 · see citing works
Targeting acetylcholinesterase and butyrylcholinesterase in dementia
Lane, R. M., Potkin, S. G., & Enz, A. (2005) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705005833 · Cited by 654 · see citing works
Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:
Grossberg, G. T. (2003) · Current Therapeutic Research · doi:10.1016/s0011-393x(03)00059-6 · Cited by 384 · see citing works
Sharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331 · see citing works
A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease
Nordberg, A., Ballard, C., Bullock, R., Darreh-Shori, T., & Somogyi, M. (2013) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.12r01412 · Cited by 323 · see citing works
Ballard, C., Sauter, M., Scheltens, P., He, Y., Barkhof, F., van Straaten, E. C. W., van der Flier, W. M., Hsu, C., Wu, S., & Lane, R. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802328142 · Cited by 147 · see citing works
Arya, A., Chahal, R., Rao, R., Rahman, M. H., Kaushik, D., Akhtar, M. F., Saleem, A., Khalifa, S. M. A., El-Seedi, H. R., Kamel, M., et al. (2021) · Biomolecules · doi:10.3390/biom11030350 · Cited by 111 · see citing works
Rivastigmine in subcortical vascular dementia
Moretti, R., Torre, P., Antonello, R. M., Cazzato, G., & Bava, A. (2002) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(02)00280-0 · Cited by 107 · see citing works
Butyrylcholinesterase and the cholinergic system
Reid, G. A., Chilukuri, N., & Darvesh, S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.054 · Cited by 105 · see citing works
Costa, P., Grosso, C., Gonçalves, S., Andrade, P. B., Valentão, P., Gabriela Bernardo-Gil, M., & Romano, A. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.04.108 · Cited by 73 · see citing works
Korábečný, J., Nepovimová, E., Cikánková, T., Špilovská, K., Vašková, L., Mezeiová, E., Kuča, K., & Hroudová, J. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2017.06.034 · Cited by 64 · see citing works
- Authors
- Mesulam, M., Guillozet, A., Shaw, P., & Quinn, B.
- Affiliations
- Northwestern University (US)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 9
- Issue
- 1
- Pages
- 88-93
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2039595489
- Cited by
- 314
- References
- 20
- Citations by year
- 2026: 9 · 2025: 25 · 2024: 17 · 2023: 14 · 2022: 20 · 2021: 21 · 2020: 14 · 2019: 9 · 2018: 16 · 2017: 14 · 2016: 18 · 2015: 8 · 2014: 5 · 2013: 9 · 2012: 11
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Exelon Corporation
- National Institutes of Health (5r01ns020285-15)
- National Institute on Aging (AG13854, P30AG013854)
- National Institute of Neurological Disorders and Stroke (NS 20285)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- butyrylcholinesterase, acetylcholine hydrolysis, acetylthiocholine, cholinergic neurotransmission, Alzheimer's disease, hippocampus, neocortex, glial cells, enzyme histochemistry, cholinesterase inhibition
- MeSH terms
- Acetylcholine, Acetylcholinesterase, Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Butyrylcholinesterase, Cholinergic Fibers, Female, Hippocampus, Humans, Hydrolysis, Neuroglia, Temporal Lobe
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