Serum microRNAs in sporadic amyotrophic lateral sclerosis
Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial a...
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Veröffentlicht in: | Neurobiology of aging 2015-09, Vol.36 (9), p.2660.e15-2660.e20 |
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creator | Freischmidt, Axel Müller, Kathrin Zondler, Lisa Weydt, Patrick Mayer, Benjamin von Arnim, Christine A.F Hübers, Annemarie Dorst, Johannes Otto, Markus Holzmann, Karlheinz Ludolph, Albert C Danzer, Karin M Weishaupt, Jochen H |
description | Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments. |
doi_str_mv | 10.1016/j.neurobiolaging.2015.06.003 |
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Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/j.neurobiolaging.2015.06.003</identifier><identifier>PMID: 26142125</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - blood ; Amyotrophic Lateral Sclerosis - genetics ; Biomarker ; Cluster Analysis ; Cohort Studies ; Computational Biology ; Diagnosis ; Down-Regulation ; Female ; Gene Expression Regulation ; Humans ; Internal Medicine ; Male ; Microarray Analysis ; MicroRNA ; MicroRNAs - blood ; MicroRNAs - genetics ; Mutation ; Neurology ; RNA, Messenger - metabolism ; Serum</subject><ispartof>Neurobiology of aging, 2015-09, Vol.36 (9), p.2660.e15-2660.e20</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-74c3a6c26370baf4e794adab060b29812fe7ee601bc4f3ce4e019c9f836362293</citedby><cites>FETCH-LOGICAL-c581t-74c3a6c26370baf4e794adab060b29812fe7ee601bc4f3ce4e019c9f836362293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0197458015003140$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26142125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freischmidt, Axel</creatorcontrib><creatorcontrib>Müller, Kathrin</creatorcontrib><creatorcontrib>Zondler, Lisa</creatorcontrib><creatorcontrib>Weydt, Patrick</creatorcontrib><creatorcontrib>Mayer, Benjamin</creatorcontrib><creatorcontrib>von Arnim, Christine A.F</creatorcontrib><creatorcontrib>Hübers, Annemarie</creatorcontrib><creatorcontrib>Dorst, Johannes</creatorcontrib><creatorcontrib>Otto, Markus</creatorcontrib><creatorcontrib>Holzmann, Karlheinz</creatorcontrib><creatorcontrib>Ludolph, Albert C</creatorcontrib><creatorcontrib>Danzer, Karin M</creatorcontrib><creatorcontrib>Weishaupt, Jochen H</creatorcontrib><title>Serum microRNAs in sporadic amyotrophic lateral sclerosis</title><title>Neurobiology of aging</title><addtitle>Neurobiol Aging</addtitle><description>Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - blood</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Biomarker</subject><subject>Cluster Analysis</subject><subject>Cohort Studies</subject><subject>Computational Biology</subject><subject>Diagnosis</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Microarray Analysis</subject><subject>MicroRNA</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Mutation</subject><subject>Neurology</subject><subject>RNA, Messenger - metabolism</subject><subject>Serum</subject><issn>0197-4580</issn><issn>1558-1497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFv1DAQhS0EotvCX0A5cOCSMGM7diIhpKqiFKmiUgtny3EmxUsSL3aCtP8er7Yg0VNPM4f3ZuZ9w9hbhAoB1fttNdMaQ-fDaO_9fF9xwLoCVQGIZ2yDdd2UKFv9nG0AW13KuoETdprSFgC01OolO-EKJUdeb1h7R3Gdism7GG6_nqfCz0XahWh77wo77cMSw-5H7ke7ULRjkdxIMSSfXrEXgx0TvX6oZ-z75advF1fl9c3nLxfn16WrG1xKLZ2wynElNHR2kKRbaXvbgYKOtw3ygTSRAuycHIQjSflq1w6NUEJx3ooz9u44dxfDr5XSYiafHI2jnSmsyaAGFLwG2WTph6M0h0kp0mB20U827g2COcAzW_M_PHOAZ0CZDC_b3zxsWruJ-n_mv7Sy4PIooJz3t6dokvM0O-p9JLeYPvinbvr4aJAb_eydHX_SntI2rHHOTA2axA2Yu8MjD3_EOrtRgvgDCQGdlw</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Freischmidt, Axel</creator><creator>Müller, Kathrin</creator><creator>Zondler, Lisa</creator><creator>Weydt, Patrick</creator><creator>Mayer, Benjamin</creator><creator>von Arnim, Christine A.F</creator><creator>Hübers, Annemarie</creator><creator>Dorst, Johannes</creator><creator>Otto, Markus</creator><creator>Holzmann, Karlheinz</creator><creator>Ludolph, Albert C</creator><creator>Danzer, Karin M</creator><creator>Weishaupt, Jochen H</creator><general>Elsevier Inc</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>20150901</creationdate><title>Serum microRNAs in sporadic amyotrophic lateral sclerosis</title><author>Freischmidt, Axel ; Müller, Kathrin ; Zondler, Lisa ; Weydt, Patrick ; Mayer, Benjamin ; von Arnim, Christine A.F ; Hübers, Annemarie ; Dorst, Johannes ; Otto, Markus ; Holzmann, Karlheinz ; Ludolph, Albert C ; Danzer, Karin M ; Weishaupt, Jochen H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c581t-74c3a6c26370baf4e794adab060b29812fe7ee601bc4f3ce4e019c9f836362293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Amyotrophic lateral sclerosis</topic><topic>Amyotrophic Lateral Sclerosis - blood</topic><topic>Amyotrophic Lateral Sclerosis - genetics</topic><topic>Biomarker</topic><topic>Cluster Analysis</topic><topic>Cohort Studies</topic><topic>Computational Biology</topic><topic>Diagnosis</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Microarray Analysis</topic><topic>MicroRNA</topic><topic>MicroRNAs - blood</topic><topic>MicroRNAs - genetics</topic><topic>Mutation</topic><topic>Neurology</topic><topic>RNA, Messenger - metabolism</topic><topic>Serum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freischmidt, Axel</creatorcontrib><creatorcontrib>Müller, Kathrin</creatorcontrib><creatorcontrib>Zondler, Lisa</creatorcontrib><creatorcontrib>Weydt, Patrick</creatorcontrib><creatorcontrib>Mayer, Benjamin</creatorcontrib><creatorcontrib>von Arnim, Christine A.F</creatorcontrib><creatorcontrib>Hübers, Annemarie</creatorcontrib><creatorcontrib>Dorst, Johannes</creatorcontrib><creatorcontrib>Otto, Markus</creatorcontrib><creatorcontrib>Holzmann, Karlheinz</creatorcontrib><creatorcontrib>Ludolph, Albert C</creatorcontrib><creatorcontrib>Danzer, Karin M</creatorcontrib><creatorcontrib>Weishaupt, Jochen H</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>Neurobiology of aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freischmidt, Axel</au><au>Müller, Kathrin</au><au>Zondler, Lisa</au><au>Weydt, Patrick</au><au>Mayer, Benjamin</au><au>von Arnim, Christine A.F</au><au>Hübers, Annemarie</au><au>Dorst, Johannes</au><au>Otto, Markus</au><au>Holzmann, Karlheinz</au><au>Ludolph, Albert C</au><au>Danzer, Karin M</au><au>Weishaupt, Jochen H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum microRNAs in sporadic amyotrophic lateral sclerosis</atitle><jtitle>Neurobiology of aging</jtitle><addtitle>Neurobiol Aging</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>36</volume><issue>9</issue><spage>2660.e15</spage><epage>2660.e20</epage><pages>2660.e15-2660.e20</pages><issn>0197-4580</issn><eissn>1558-1497</eissn><abstract>Abstract MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and specific mircoRNA “fingerprints” are thought to contribute to and/or reflect certain disease conditions. Recently, we identified surprisingly homogeneous signatures of circulating miRNAs in the serum of familial amyotrophic lateral sclerosis (ALS) patients, which were already present in presymptomatic carriers of ALS gene mutations. Here, we characterize circulating miRNAs in the serum of sporadic ALS patients. We show that, in contrast to familial ALS, miRNA signatures of sporadic ALS are highly heterogeneous suggesting a number of different etiologies. Nevertheless, 2 miRNAs, miR-1234-3p and miR-1825, could be identified to be consistently downregulated in sporadic ALS. Bioinformatic analysis revealed miRNA fingerprints resembling those of familial ALS patients and mutation carriers in 61% of sporadic ALS patients, while the remaining subgroup had clearly different miRNA signatures. These data support a higher than expected contribution of genetic factors also to sporadic ALS. Moreover, our results indicate a more heterogeneous molecular etiology of sporadic ALS compared with (mono)genic cases, which should be considered for the development of disease modifying treatments.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26142125</pmid><doi>10.1016/j.neurobiolaging.2015.06.003</doi></addata></record> |
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subjects | Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - blood Amyotrophic Lateral Sclerosis - genetics Biomarker Cluster Analysis Cohort Studies Computational Biology Diagnosis Down-Regulation Female Gene Expression Regulation Humans Internal Medicine Male Microarray Analysis MicroRNA MicroRNAs - blood MicroRNAs - genetics Mutation Neurology RNA, Messenger - metabolism Serum |
title | Serum microRNAs in sporadic amyotrophic lateral sclerosis |
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