Changes in arginine metabolism in advanced Alzheimer?s patients: Experimental and theoretical analyses

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dc.authoridErsan, Etem Erdal/0000-0002-7104-2908
dc.authoridSari, Ismail/0000-0003-3732-2102
dc.authoridBerisha, Avni/0000-0002-3876-1345
dc.contributor.authorSaria, Ismail
dc.contributor.authorErsan, Serpil
dc.contributor.authorOzmen, Esma
dc.contributor.authorAyan, Durmus
dc.contributor.authorErsan, Erdal
dc.contributor.authorBerisha, Avni
dc.contributor.authorKayae, Savas
dc.date.accessioned2024-11-07T13:34:04Z
dc.date.available2024-11-07T13:34:04Z
dc.date.issued2023
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractLimited data obtained in studies conducted in recent years suggest that changes in arginine metabolism may be associated with the pathogenesis of Alzheimer's disease (AD). However, the underlying mecha-nisms of this pathway's effects on the disease are not clear and there are conflicting data. Therefore, in this study, we aimed to determine the levels of L-arginine and its important metabolites and enzymes involved in the pathway in advanced AD patients to examine the change in L-arginine metabolism as inclusively as possible.Serum and plasma samples were obtained from 51 patients diagnosed with advanced AD and 30 volunteer controls. Arginase, Ornithine Decarboxylase (ODC), Arginine Decarboxylase (ADC), and Agmati-nase levels in serum samples were determined by enzyme-linked immunosorbent assay (ELISA) and, L- arginine, Ornithine and nitric oxide (NO) levels were determined by colorimetric method. Agmatine levels were measured by high-performance liquid chromatography in the plasma samples of the study groups. Furthermore, in silico molecular docking studies were performed to get preliminary knowledge about the binding interactions of the agmatine with various targets such as AChE, butyrylcholinesterase (BuChE), BACE-1 and tau protein kinase 1 which play an important role in AD pathogenesis.Agmatine and L-arginine levels were found to be significantly lower in the patient group than in the control group. Milder but not statistically significant reductions were observed in all other param-eters we measured involved in L-arginine metabolism. Furthermore, NO levels were found to be sig-nificantly lower in men with advanced AD patients than in control men. It has been analyzed that agmatine ligand interacts effectively with the studied proteins which play an important role in AD pathogenesis; these interactions were significant and, based on the docking score, occurred in the fol-lowing order: butyrylcholinesterase (PDB id: 1P0I) > Human acetylcholinesterase > Human tau-protein kinase I.In conclusion, in advanced AD patients, the activity of the L-arginine pathway decreased in gen-eral, especially agmatine formation, and this may be due to the decrease in L-arginine levels. Therefore, arginine de novo synthesis may be decreased in advanced AD patients. Furthermore, according to the MolDock binding score, agmatine ligand has a high binding affinity for proteins involved in AD manage-ment and/or pathogenesis. Therefore, agmatine may play a role in the pathogenesis of AD by inhibit-ing the activity of these proteins. However, additional comprehensive studies are needed to clarify these thoughts.(c) 2023 Elsevier B.V. All rights reserved.
dc.description.sponsorshipNi g?de ?; mer Halisdemir Univer- sity Scientific Research Projects Coordination Unit [SAT 2020/4-BAGEP]
dc.description.sponsorshipThis work was supported by the Ni g?de ?mer Halisdemir Univer- sity Scientific Research Projects Coordination Unit (grant number: SAT 2020/4-BAGEP) .
dc.identifier.doi10.1016/j.molstruc.2023.135254
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-85149416064
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2023.135254
dc.identifier.urihttps://hdl.handle.net/11480/15765
dc.identifier.volume1282
dc.identifier.wosWOS:000950769500001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241106
dc.subjectAlzheimer?s disease
dc.subjectAgmatine
dc.subjectL -arginine metabolism
dc.subjectNitric oxide
dc.titleChanges in arginine metabolism in advanced Alzheimer?s patients: Experimental and theoretical analyses
dc.typeArticle

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