Aim: In the present study, the effect of donepezil hydrochloride was studied on the transgenic expressing human amyloid beta-42 in the neurons.
Methods: Donepezil hydrochloride at final concentration of 0.1, 1 and 10 mM was mixed in the diet and the flies expressing human amyloid beta-42 under Upstream Activation Sequence control (Alzheimer Disease [AD] flies) were allowed to feed on it for 30 days.
Results: The AD flies exposed to various doses of Donepezil hydrochloride showed a dose dependent significant delay in the loss of climbing ability, increase in activity, reduction in the oxidative stress and apoptotic markers. A significant improvement was also observed in cognitive parameters. A dose dependent significant reduction in the activity of acetylcholinesterase was also observed. The docking studies suggest the positive interaction between donepezil, amyloid beta-42 and acetylcholinesterase. The results obtained from immunohistochemistry also showed a dose dependent significant reduction in the amyloid beta-42 aggregates.
Conclusion: The results suggest that donepezil hydrochloride is potent enough to reduce the AD symptoms being mimicked in transgenic flies.
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http://dx.doi.org/10.1080/00207454.2023.2262109 | DOI Listing |
Pharmaceutics
January 2025
Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Mexico City 14269, Mexico.
Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored.
View Article and Find Full Text PDFPharmaceutics
January 2025
BK21 FOUR KNU Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
: Although donepezil, a reversible acetylcholinesterase inhibitor, has been in use since 1996, its metabolic characteristics remain poorly characterized. Therefore, this study aims to investigate the in vivo metabolism of donepezil using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) based on a molecular networking (MN) approach integrated with a non-targeted metabolomics approach. : After the oral administration of donepezil (30 mg/kg) in rats, urine, feces, and liver samples were collected for LC-HRMS analysis.
View Article and Find Full Text PDFPharmaceutics
January 2025
Laboratory of Advanced Pharmaceutical Process Engineering, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan.
: Orally disintegrating film (ODF) is prepared using water-soluble polymers as film-forming agents. To improve mechanical and disintegration properties, some polymers need to be blended with others. This study aimed to investigate the utility of hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC) as blend film-forming components for ODFs.
View Article and Find Full Text PDFBehav Brain Res
January 2025
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Von-Siebold-Str. 5, 37075 Göttingen, Germany.
Background: Neural autoantibodies are being increasingly detected in conjunction with neurodegenerative dementias such as Alzheimer's disease dementia (AD), yet their significance is not well clarified. In this case report, we report the previously unreported long-lasting persistence of potassium voltage-gated channel subfamily A member 2 (KCNA2) antibodies in biomarker-supported AD.
Methods: We report on a 77-year-old, male patient evaluated in our outpatient memory clinic of the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen.
J Neurophysiol
January 2025
Dept of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Deep brain stimulation (DBS) using electrical stimulation of neuronal tissue in the basal forebrain to enhance release of the neurotransmitter acetylcholine is under consideration to improve executive function in patients with dementia. While some small studies indicate a positive response in the clinical setting, the relationship between DBS and acetylcholine pharmacokinetics is incompletely understood. We examined the cortical acetylcholine response to different stimulation parameters of the basal forebrain.
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