title: Selenomethionine reduces the deposition of beta-amyloid plaques by modulating β-secretase and enhancing selenoenzymatic activity in a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by the production of large amounts of beta-amyloid (Aβ) and the accumulation of extracellular senile plaques, which have been considered to be potential targets in the treatment of AD. Selenium (Se) is a nutritionally essential trace element with known antioxidant potential and Se status has been shown to decrease with age and has a close relationship with cognitive competence in AD. Selenomethionine (Se-Met), a major reserve form of Se in organisms, has been shown in our previous study to ameliorate the decline in cognitive function, increase oxidation resistance, and reduce tau hyperphosphorylation in a triple transgenic mouse model of AD. However, it has not been reported whether Se-Met has any effects on Aβ pathology in AD mice. To study the effect of Se-Met on Aβ pathology and the function of selenoproteins/selenoenzymes in 3× Tg-AD mice, 3× Tg-AD mice at 8 months of age were treated with Se-Met for 3 months. Se-Met led to significantly reduced production and deposition of Aβ, down-regulation of β-secretase levels and enhanced activity of selenoenzymes as well as increased levels of Se in the hippocampus and cortex. Se-Met reduces amyloidogenic processing of amyloid precursor protein while modulating β-secretase and selenoenzymatic activity in AD mice. These results indicate that Se-Met might exert its therapeutic effect through multiple pathways in AD.
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Changchun, China.
authors.forename: Zhong-Hao
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Changchun, China and Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Jia-Zuan
authors.initials: JZ
authors.lastname: Ni
authors.affiliation: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hoffmann
authors.affiliation: Shenzhen Key Laboratory of Marine Bioresources and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China. lilys@szu.edu.cn.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Song
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012645:Selenomethionine / Q000494:pharmacology*; D051140:Selenoproteins / Q000378:metabolism*
chemical_list: D051140:Selenoproteins; D012645:Selenomethionine; D053829:Amyloid Precursor Protein Secretases