Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly
The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a Drosophila (fruitfly) model of AD in which the flies overexpress the human Aβ 42 peptide. We identified 712 genes that...
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| Veröffentlicht in: | Scientific reports 2013-12, Vol.3 (1), p.3512, Article 3512 |
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| creator | Favrin, G. Bean, D. M. Bilsland, E. Boyer, H. Fischer, B. E. Russell, S. Crowther, D. C. Baylis, H. A. Oliver, S. G. Giannakou, M. E. |
| description | The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a
Drosophila
(fruitfly) model of AD in which the flies overexpress the human Aβ
42
peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b. |
| doi_str_mv | 10.1038/srep03512 |
| format | Article |
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Drosophila
(fruitfly) model of AD in which the flies overexpress the human Aβ
42
peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep03512</identifier><identifier>PMID: 24336499</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/61 ; 38/89 ; 631/208/199 ; 631/378/1689/1283 ; 631/378/2611 ; 631/553/1833 ; 64/24 ; Aging ; Amyloid beta-Peptides - toxicity ; Animals ; Cluster Analysis ; Computational Biology ; Drosophila - drug effects ; Drosophila - genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Humanities and Social Sciences ; Immunity, Innate - genetics ; Male ; Molecular Chaperones - genetics ; multidisciplinary ; Oxidative Stress - genetics ; Phenotype ; RNA Interference ; Science ; Transcriptome</subject><ispartof>Scientific reports, 2013-12, Vol.3 (1), p.3512, Article 3512</ispartof><rights>The Author(s) 2013</rights><rights>Copyright © 2013, Macmillan Publishers Limited. All rights reserved 2013 Macmillan Publishers Limited. All rights reserved</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-ff41c57f31ae443a4a059e484d9db84a4d1b4d23ada6f83ee1ab995965c8a5cd3</citedby><cites>FETCH-LOGICAL-c410t-ff41c57f31ae443a4a059e484d9db84a4d1b4d23ada6f83ee1ab995965c8a5cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863820/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863820/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24336499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Favrin, G.</creatorcontrib><creatorcontrib>Bean, D. M.</creatorcontrib><creatorcontrib>Bilsland, E.</creatorcontrib><creatorcontrib>Boyer, H.</creatorcontrib><creatorcontrib>Fischer, B. E.</creatorcontrib><creatorcontrib>Russell, S.</creatorcontrib><creatorcontrib>Crowther, D. C.</creatorcontrib><creatorcontrib>Baylis, H. A.</creatorcontrib><creatorcontrib>Oliver, S. G.</creatorcontrib><creatorcontrib>Giannakou, M. E.</creatorcontrib><title>Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a
Drosophila
(fruitfly) model of AD in which the flies overexpress the human Aβ
42
peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b.</description><subject>38/61</subject><subject>38/89</subject><subject>631/208/199</subject><subject>631/378/1689/1283</subject><subject>631/378/2611</subject><subject>631/553/1833</subject><subject>64/24</subject><subject>Aging</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Animals</subject><subject>Cluster Analysis</subject><subject>Computational Biology</subject><subject>Drosophila - drug effects</subject><subject>Drosophila - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Immunity, Innate - genetics</subject><subject>Male</subject><subject>Molecular Chaperones - genetics</subject><subject>multidisciplinary</subject><subject>Oxidative Stress - genetics</subject><subject>Phenotype</subject><subject>RNA Interference</subject><subject>Science</subject><subject>Transcriptome</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNptkd1KHTEUhYO0qNhz4QuUXLbC0fzNdHJTEKlWELzROyHsyY9GZpLTJCOd1_JBfCYj5_Sg0NwkrP2x9s7aCB1SckwJ705ysivCG8p20D4jolkyztind-89tMj5kdTTMCmo3EV7THDeCin30d2lsaF45zUUHwOODof4ZAc8RlNVm_KbdPryjEv867UvM-5nXBKErJNflTh6jSHAMGefsQ-4PFjs0uSLG-Yv6LODIdvF5j5At-e_bs5-L6-uLy7PTq-WWlBSls4JqpsfjlOwQnAQQBppRSeMNH0nQBjaC8M4GGhdx62l0EvZyLbRHTTa8AP0c-27mvrRGl1_lGBQq-RHSLOK4NXHSvAP6j4-Kd61vGOkGnzbGKT4Z7K5qNFnbYcBgo1TVlS0klFCqajo9zWqU8w1e7dtQ4l6W4jaLqSyX9_PtSX_xV-BozWQaync26Qe45Rqmvk_bq9gE5hi</recordid><startdate>20131216</startdate><enddate>20131216</enddate><creator>Favrin, G.</creator><creator>Bean, D. M.</creator><creator>Bilsland, E.</creator><creator>Boyer, H.</creator><creator>Fischer, B. E.</creator><creator>Russell, S.</creator><creator>Crowther, D. C.</creator><creator>Baylis, H. A.</creator><creator>Oliver, S. G.</creator><creator>Giannakou, M. E.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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><scope>5PM</scope></search><sort><creationdate>20131216</creationdate><title>Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly</title><author>Favrin, G. ; Bean, D. M. ; Bilsland, E. ; Boyer, H. ; Fischer, B. E. ; Russell, S. ; Crowther, D. C. ; Baylis, H. A. ; Oliver, S. G. ; Giannakou, M. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-ff41c57f31ae443a4a059e484d9db84a4d1b4d23ada6f83ee1ab995965c8a5cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>38/61</topic><topic>38/89</topic><topic>631/208/199</topic><topic>631/378/1689/1283</topic><topic>631/378/2611</topic><topic>631/553/1833</topic><topic>64/24</topic><topic>Aging</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Animals</topic><topic>Cluster Analysis</topic><topic>Computational Biology</topic><topic>Drosophila - drug effects</topic><topic>Drosophila - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humanities and Social Sciences</topic><topic>Immunity, Innate - genetics</topic><topic>Male</topic><topic>Molecular Chaperones - genetics</topic><topic>multidisciplinary</topic><topic>Oxidative Stress - genetics</topic><topic>Phenotype</topic><topic>RNA Interference</topic><topic>Science</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Favrin, G.</creatorcontrib><creatorcontrib>Bean, D. M.</creatorcontrib><creatorcontrib>Bilsland, E.</creatorcontrib><creatorcontrib>Boyer, H.</creatorcontrib><creatorcontrib>Fischer, B. E.</creatorcontrib><creatorcontrib>Russell, S.</creatorcontrib><creatorcontrib>Crowther, D. C.</creatorcontrib><creatorcontrib>Baylis, H. A.</creatorcontrib><creatorcontrib>Oliver, S. G.</creatorcontrib><creatorcontrib>Giannakou, M. E.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Favrin, G.</au><au>Bean, D. M.</au><au>Bilsland, E.</au><au>Boyer, H.</au><au>Fischer, B. E.</au><au>Russell, S.</au><au>Crowther, D. C.</au><au>Baylis, H. A.</au><au>Oliver, S. G.</au><au>Giannakou, M. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2013-12-16</date><risdate>2013</risdate><volume>3</volume><issue>1</issue><spage>3512</spage><pages>3512-</pages><artnum>3512</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a
Drosophila
(fruitfly) model of AD in which the flies overexpress the human Aβ
42
peptide. We identified 712 genes that are differentially expressed between control and Aβ-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aβ phenotype, namely Sod3 and PGRP-SC1b.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24336499</pmid><doi>10.1038/srep03512</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 38/61 38/89 631/208/199 631/378/1689/1283 631/378/2611 631/553/1833 64/24 Aging Amyloid beta-Peptides - toxicity Animals Cluster Analysis Computational Biology Drosophila - drug effects Drosophila - genetics Female Gene Expression Profiling Gene Expression Regulation - drug effects Humanities and Social Sciences Immunity, Innate - genetics Male Molecular Chaperones - genetics multidisciplinary Oxidative Stress - genetics Phenotype RNA Interference Science Transcriptome |
| title | Identification of novel modifiers of Aβ toxicity by transcriptomic analysis in the fruitfly |
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