Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Weiwei LinXiaomei Ling

Abstract

Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and treatment are not sufficient so far. The purpose of this study is to develop biomarkers and therapeutic targets for diagnosis and better understanding of AD. As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF-MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD hippocampus by using label free nano-LC-MS/MS. Thus, pathogenesis of AD was involved with increasing of choline, decreasing of ACh, enhancement of GSTs and increasing of glutamate which led to oxidative stress and excitotoxity. Effects of donepezil and a natural medicine were evaluated through metabolomics and proteomics. In summary, proteomic and metabolomic analysis on constructed AD rat model were performed through rapid, sensitive and high resolution LC-MS methods to reveal candidate biomarkers. The data suggested that GSTs have great value as therapeutic targets. This study provided valuable in...Continue Reading

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Citations

Sep 1, 2018·Clinical Chemistry and Laboratory Medicine : CCLM·Zikuan SongWei Jiang
Dec 24, 2018·Proteomics. Clinical Applications·Gajanan SatheAkhilesh Pandey
Mar 9, 2019·International Journal of Molecular Sciences·Shi-Hui LawLiang-Yin Ke
Jan 1, 2020·Brain : a Journal of Neurology·AmanPreet BadhwarPierre Bellec
Jan 4, 2020·Mass Spectrometry Reviews·Giuseppe Grasso
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Mingyong ZhangYifeng Chai
Dec 14, 2018·Cellular and Molecular Life Sciences : CMLS·Ruth R MagayeBing H Wang
Mar 17, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Eva KnuplezGunther Marsche
Aug 17, 2021·Journal of Alzheimer's Disease : JAD·Gianna FoteHoward J Federoff
Apr 22, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jianmei ZhangXiaomei Ling

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