It has been established that the non-neuronal cholinergic system is related to the oncogenesis which increases the attractiveness of its components as the promising markers of oncologic diseases. The purpose of this work is to evaluate the clinical significance of the analysis of the activity of acetyl cholinesterase as a new marker of gliomas. The activity of acetyl cholinesterase was assessed by photo colorimetric analysis according to the Hestrin method recalculating the activity of the enzyme in the tumor tissue per 1 g of protein, and in the blood - by 0.1 g of hemoglobin. The data obtained in the primary tumors of the brain (28) in the tissue of the brain of persons who died as a result of injury (6) and in whole blood of patients with gliomas (28) and practically healthy people (10) were compared with the use of a number of statistical programs. A significant decrease in the activity of acetyl cholinesterase in tumor tissue and in whole blood is revealed as the degree of anaplasia of tumors increases, starting with Grade II. It is for the first time that a significant direct correlation was noted showing the consistency between the decrease in the activity of acetyl cholinesterase in the tumor tissue of the brain and blood. Bioinformatic analysis showed the connection of the enzyme of acetyl cholinesterase with proteins of the PI3K-AKT and Notch signaling pathways providing antiapoptotic and proliferative effects. The found dependences provide new insights into understanding of the mechanisms of gliomas genesis and can be used for selection of new diagnostic markers of brain tumors.
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http://dx.doi.org/10.51620/0869-2084-2021-66-12-718-721 | DOI Listing |
Cell Mol Neurobiol
December 2024
Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and memory deficit. Even with extensive research and studies, presently, there is no effective treatment for the management of AD. Besides, most of drugs used in the treatment of AD did not avert the AD neuropathology, and the disease still in a progressive status.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer's disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with -phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD.
View Article and Find Full Text PDFJ Enzyme Inhib Med Chem
December 2024
Faculty of Food and Technology Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and -acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of β-amyloid plaques by inhibiting both the β-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants (i) in micromolar range able to lower the activity of β-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants.
View Article and Find Full Text PDFEcotoxicol Environ Saf
November 2024
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
European honey bee (Apis mellifera L.) is an essential pollinator that contributes significantly to the global ecosystem and agricultural productivity. However, their population has been facing unprecedented threats, primarily due to their exposure to various pesticides, including organophosphates.
View Article and Find Full Text PDFPhytother Res
January 2025
Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Pozzuoli (NA), Italy.
Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model.
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