There is evidence to suggest an involvement of the K variant of the butyrylcholinesterase gene (BCHE) in dementia. We have examined the relationship between BCHE genotype and butyrylcholinesterase (BuChE) activity in autopsy brain tissue. We studied 164 autopsy cases, 144 with dementia and 20 controls, including 13 K homozygotes and 48 K heterozygotes, from three centres: Newcastle, Oxford and London. Mean BuChE activity in temporal cortex was 37% higher in K homozygotes than in wild-type homozygotes. Linear regression analysis, controlling for gender, diagnosis, age at death and study centre, showed that the number of BCHE-K alleles was associated with increasing BuChE activity (p=0.009).
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http://dx.doi.org/10.1016/j.neulet.2008.07.023 | DOI Listing |
Biochem Res Int
December 2024
Kentucky College of Osteopathic Medicine, University of Pikeville, Pikeville 41501, Kentucky, USA.
Alzheimer's disease (AD), a neurological disorder, is one of the major reasons for memory loss in the world. AD is characterized by a sequela of cognitive and functional decline caused by brain cell degeneration. Paeoniflorin is a monoterpenoid glycoside found in plants of the Paeoniaceae family, which are known for their medicinal properties including dementia.
View Article and Find Full Text PDFHeliyon
December 2024
Medicinal Chemistry Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Alzheimer's disease (AD), a chronic neurodegenerative disease, is clinically characterized by loss of memory and learning ability among other neurological deficits. Amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles involve in AD etiology. Meanwhile, enzymes and their inhibitors have become the focus of research in AD treatment.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo, 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria, 21648, Egypt. Electronic address:
As a complicated neurodegenerative disorder with several clinical hallmarks, Alzheimer's disease (AD) requires multi-target treatment medicines to address multiple elements of disease progression. In this study, we reported two novel series of compounds: benzofuran-based donepezil analogs (9a-i) and their pyrazole-based counterparts (11a-i) as potential dual inhibitors of AChE and BuChE with additional antioxidant properties, aiming to address multiple pathological aspects of AD simultaneously. The design strategy employed bioisosteric replacement, substituting donepezil's indanone motif with a benzofuran ring in series (9a-i) to maintain crucial hydrogen bonding interactions with the Phe295 residue in the enzyme's active site.
View Article and Find Full Text PDFOrg Biomol Chem
December 2024
Centro de Química Estrutural, Institute for Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
The computational study of the most relevant interactions of the nanomolar purine nucleoside BuChE selective inhibitor has shown that the benzyl group at position 2 and the purine acetamido group are required for activity. In addition, the synthesis of a 6-iodinated radiolabelled analogue and the study of bioavailability have shown a low percentage of uptake by the brain after 1 hour. These results encouraged the synthesis of a small library of new compounds, focussing on deoxygenation at other positions aiming to access active and more bioavailable structures.
View Article and Find Full Text PDFFuture Med Chem
December 2024
Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical, Chennai, Tamil Nadu, India.
Aim: Nitrogen and sulfur-containing compounds are the core components utilized for synthesis of different heterocyclic moieties.
Methods & Results: In this research, a series of new analogues containing thiazolidinone have been synthesized in order to evaluate their activity against acetylcholinesterase and butyrylcholinesterase. Potent analogues were further subjected for molecular docking in order to study their protein-ligand interactions.
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