دورية أكاديمية
Methionine oxidation of clusterin in Alzheimer's disease and its effect on clusterin's binding to beta-amyloid.
| العنوان: | Methionine oxidation of clusterin in Alzheimer's disease and its effect on clusterin's binding to beta-amyloid. |
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| المؤلفون: | Smith AS; Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA., Subramanian J; Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA., Doderer J; Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA., Moskovitz J; Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA. Electronic address: moskovij@ku.edu. |
| المصدر: | Neuroscience letters [Neurosci Lett] 2024 Jul 27; Vol. 836, pp. 137874. Date of Electronic Publication: 2024 Jun 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Scientific Publishers Ireland Country of Publication: Ireland NLM ID: 7600130 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7972 (Electronic) Linking ISSN: 03043940 NLM ISO Abbreviation: Neurosci Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Scientific Publishers Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
| مواضيع طبية MeSH: | Clusterin*/metabolism , Alzheimer Disease*/metabolism , Alzheimer Disease*/pathology , Methionine*/metabolism , Methionine*/analogs & derivatives , Amyloid beta-Peptides*/metabolism , Oxidation-Reduction* , Brain*/metabolism , Astrocytes*/metabolism, Humans ; Animals ; Mice ; Neurons/metabolism ; Protein Binding ; Male ; Aged |
| مستخلص: | Clusterin is a secreted glycoprotein that participates in multiple physiological processes through its chaperon function. In Alzheimer's disease, the brain functions under an increased oxidative stress condition that causes an elevation of protein oxidation, resulting in enhanced pathology. Accordingly, it is important to determine the type of human brain cells that are mostly prone to methionine oxidation in Alzheimer's disease and specifically monitoring the methionine-oxidation levels of clusterin in human and mice brains and its effect on clusterin's function. We analyzed the level of methionine sulfoxide (MetO)-clusterin in these brains, using a combination of immunoprecipitation and Western-blott analyses. Also, we determine the effect of methionine oxidation on clusterin ability to bind beta-amyloid, in vitro, using calorimetric assay. Our results show that human neurons and astrocytes of Alzheimer's disease brains are mostly affected by methionine oxidation. Moreover, MetO-clusterin levels are elevated in postmortem Alzheimer's disease human and mouse brains in comparison to controls. Finally, oxidation of methionine residues of purified clusterin reduced its binding efficiency to beta-amyloid. In conclusion, we suggest that methionine oxidation of brain-clusterin is enhanced in Alzheimer's disease and that this oxidation compromises its chaperon function, leading to exacerbation of beta-amyloid's toxicity in Alzheimer's disease. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Neurodegenerative diseases; Oxidative stress; Protein oxidation |
| المشرفين على المادة: | 0 (Clusterin) AE28F7PNPL (Methionine) 0 (Amyloid beta-Peptides) XN1XVI4B2C (methionine sulfoxide) |
| تواريخ الأحداث: | Date Created: 20240610 Date Completed: 20240722 Latest Revision: 20240722 |
| رمز التحديث: | 20240723 |
| DOI: | 10.1016/j.neulet.2024.137874 |
| PMID: | 38857696 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7972 |
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| DOI: | 10.1016/j.neulet.2024.137874 |