The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent
Open accessAbstract
Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra- and extracellular β-amyloid precursor protein, and secreted β-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that overexpressed human mutant amyloid precursor protein also resulted in lower β-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease.
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Cited by
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Alzheimer’s Disease: An Updated Overview of Its Genetics
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Metadata
- Authors
- Greig, N. H., Utsuki, T., Ingram, D. K., Wang, Y., Pepeu, G., Scali, C., Yu, Q.-S., Mamczarz, J., Holloway, H. W., Giordano, T., Chen, D., Furukawa, K., Sambamurti, K., Brossi, A., & Lahiri, D. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-11-07
- Volume
- 102
- Issue
- 47
- Pages
- 17213-17218
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2159866533
- Cited by
- 734
- References
- 51
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Open access
- green
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- Greig, N. H., Utsuki, T., Ingram, D. K., Wang, Y., Pepeu, G., Scali, C., Yu, Q.-S., Mamczarz, J., Holloway, H. W., Giordano, T., Chen, D., Furukawa, K., Sambamurti, K., Brossi, A., & Lahiri, D. K. (2005). Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0508575102
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