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Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease
Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of diffe...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045564/ https://www.ncbi.nlm.nih.gov/pubmed/36978950 http://dx.doi.org/10.3390/antiox12030702 |
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author | Zhang, Zhong-Hao Peng, Jia-Ying Chen, Yu-Bin Wang, Chao Chen, Chen Song, Guo-Li |
author_facet | Zhang, Zhong-Hao Peng, Jia-Ying Chen, Yu-Bin Wang, Chao Chen, Chen Song, Guo-Li |
author_sort | Zhang, Zhong-Hao |
collection | PubMed |
description | Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD. |
format | Online Article Text |
id | pubmed-10045564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100455642023-03-29 Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease Zhang, Zhong-Hao Peng, Jia-Ying Chen, Yu-Bin Wang, Chao Chen, Chen Song, Guo-Li Antioxidants (Basel) Article Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer’s disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3β) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD. MDPI 2023-03-12 /pmc/articles/PMC10045564/ /pubmed/36978950 http://dx.doi.org/10.3390/antiox12030702 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Zhong-Hao Peng, Jia-Ying Chen, Yu-Bin Wang, Chao Chen, Chen Song, Guo-Li Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title | Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title_full | Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title_fullStr | Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title_full_unstemmed | Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title_short | Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer’s Disease |
title_sort | different effects and mechanisms of selenium compounds in improving pathology in alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045564/ https://www.ncbi.nlm.nih.gov/pubmed/36978950 http://dx.doi.org/10.3390/antiox12030702 |
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