Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics
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...
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| Veröffentlicht in: | European journal of pharmaceutical sciences 2017-07, Vol.105, p.119-126 |
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| creator | Lin, Weiwei Zhang, Jianmei Liu, Yanmeng Wu, Ruijun Yang, Haisong Hu, Xiaobo Ling, Xiaomei |
| description | 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 information for the diagnosis mechanism and drug discovery of AD.
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| doi_str_mv | 10.1016/j.ejps.2017.05.003 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2017.05.003</identifier><identifier>PMID: 28495476</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Alzheimer Disease - blood ; Alzheimer Disease - diagnosis ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer's disease ; Animals ; Biomarkers ; Biomarkers - metabolism ; Cerebral Cortex - metabolism ; Cerebral Cortex - pathology ; Glutathione S-transferases ; Glutathione Transferase - metabolism ; LC-MS ; Male ; Metabolomics ; Metabonomics ; Proteomics ; Rats, Sprague-Dawley ; Sphingolipid metabolism</subject><ispartof>European journal of pharmaceutical sciences, 2017-07, Vol.105, p.119-126</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-ff70e925b731fa33c9e0caa2efe0bea9a25c705bbe9b234ed2436aef13e0ecc43</citedby><cites>FETCH-LOGICAL-c422t-ff70e925b731fa33c9e0caa2efe0bea9a25c705bbe9b234ed2436aef13e0ecc43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejps.2017.05.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28495476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Weiwei</creatorcontrib><creatorcontrib>Zhang, Jianmei</creatorcontrib><creatorcontrib>Liu, Yanmeng</creatorcontrib><creatorcontrib>Wu, Ruijun</creatorcontrib><creatorcontrib>Yang, Haisong</creatorcontrib><creatorcontrib>Hu, Xiaobo</creatorcontrib><creatorcontrib>Ling, Xiaomei</creatorcontrib><title>Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>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 information for the diagnosis mechanism and drug discovery of AD.
[Display omitted]</description><subject>Alzheimer Disease - blood</subject><subject>Alzheimer Disease - diagnosis</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Cerebral Cortex - metabolism</subject><subject>Cerebral Cortex - pathology</subject><subject>Glutathione S-transferases</subject><subject>Glutathione Transferase - metabolism</subject><subject>LC-MS</subject><subject>Male</subject><subject>Metabolomics</subject><subject>Metabonomics</subject><subject>Proteomics</subject><subject>Rats, Sprague-Dawley</subject><subject>Sphingolipid metabolism</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi1ERZfCH-CAcoNL0rGTrGOJS1XxJVXiAJytiTNpvCRx8CSV4NZ_Xi9bOHKawzzvO5pHiFcSCglyf3ko6LBwoUDqAuoCoHwidrLRJget4KnYgVFNDqbR5-I58wEA9o2GZ-JcNZWpK73fifuv69Z54izMWefxdg68epe1PkwYf1DkDOcuWweKuNB2XE3kBpw9T1nos6vx90B-oviGU5wJmRIcw3Y7JHDFNoxh8u7UMvhlCQ6nBcdsiWGlP6sX4qzHkenl47wQ3z-8_3b9Kb_58vHz9dVN7iql1rzvNZBRdatL2WNZOkPgEBX1BC2hQVU7DXXbkmlVWVGnqnKP1MuSgJyrygvx9tSbTv_ciFc7eXY0jjhT2NjKxhiZZEmVUHVCXQzMkXq7RJ98_LIS7FG9PdijentUb6G2SX0KvX7s39qJun-Rv64T8O4EUPryzlO07DzNjjofya22C_5__Q8ugZnS</recordid><startdate>20170715</startdate><enddate>20170715</enddate><creator>Lin, Weiwei</creator><creator>Zhang, Jianmei</creator><creator>Liu, Yanmeng</creator><creator>Wu, Ruijun</creator><creator>Yang, Haisong</creator><creator>Hu, Xiaobo</creator><creator>Ling, Xiaomei</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170715</creationdate><title>Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics</title><author>Lin, Weiwei ; Zhang, Jianmei ; Liu, Yanmeng ; Wu, Ruijun ; Yang, Haisong ; Hu, Xiaobo ; Ling, Xiaomei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-ff70e925b731fa33c9e0caa2efe0bea9a25c705bbe9b234ed2436aef13e0ecc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alzheimer Disease - blood</topic><topic>Alzheimer Disease - diagnosis</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Cerebral Cortex - metabolism</topic><topic>Cerebral Cortex - pathology</topic><topic>Glutathione S-transferases</topic><topic>Glutathione Transferase - metabolism</topic><topic>LC-MS</topic><topic>Male</topic><topic>Metabolomics</topic><topic>Metabonomics</topic><topic>Proteomics</topic><topic>Rats, Sprague-Dawley</topic><topic>Sphingolipid metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Weiwei</creatorcontrib><creatorcontrib>Zhang, Jianmei</creatorcontrib><creatorcontrib>Liu, Yanmeng</creatorcontrib><creatorcontrib>Wu, Ruijun</creatorcontrib><creatorcontrib>Yang, Haisong</creatorcontrib><creatorcontrib>Hu, Xiaobo</creatorcontrib><creatorcontrib>Ling, Xiaomei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Weiwei</au><au>Zhang, Jianmei</au><au>Liu, Yanmeng</au><au>Wu, Ruijun</au><au>Yang, Haisong</au><au>Hu, Xiaobo</au><au>Ling, Xiaomei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2017-07-15</date><risdate>2017</risdate><volume>105</volume><spage>119</spage><epage>126</epage><pages>119-126</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><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 information for the diagnosis mechanism and drug discovery of AD.
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| subjects | Alzheimer Disease - blood Alzheimer Disease - diagnosis Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Animals Biomarkers Biomarkers - metabolism Cerebral Cortex - metabolism Cerebral Cortex - pathology Glutathione S-transferases Glutathione Transferase - metabolism LC-MS Male Metabolomics Metabonomics Proteomics Rats, Sprague-Dawley Sphingolipid metabolism |
| title | Studies on diagnostic biomarkers and therapeutic mechanism of Alzheimer's disease through metabolomics and hippocampal proteomics |
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