000057865 001__ 57865
000057865 005__ 20170620150449.0
000057865 0247_ $$2doi$$a10.1371/journal.pone.0089065
000057865 0248_ $$2sideral$$a84847
000057865 037__ $$aART-2014-84847
000057865 041__ $$aeng
000057865 100__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne Markus$$uUniversidad de Zaragoza
000057865 245__ $$aMicroRNA-206: A Potential Circulating Biomarker Candidate for Amyotrophic Lateral Sclerosis
000057865 260__ $$c2014
000057865 5060_ $$aAccess copy available to the general public$$fUnrestricted
000057865 5203_ $$aAmyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. Biomarkers are urgently needed to facilitate ALS diagnosis and prognosis, and as indicators of therapeutic response in clinical trials. microRNAs (miRNAs), small posttranscriptional modifiers of gene expression, are frequently altered in disease conditions. Besides their important regulatory role in variety of biological processes, miRNAs can also be released into the circulation by pathologically affected tissues and display remarkable stability in body fluids. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. To find biomarkers for ALS, we studied miRNA alterations from skeletal muscle and plasma of SOD1-G93A mice, and subsequently tested the levels of the affected miRNAs in the serum from human ALS patients. Fast-twitch and slow-twitch muscles from symptomatic SOD1-G93A mice (age 90 days) and their control littermates were first studied using miRNA microarrays and then evaluated with quantitative PCR from five age groups from neonatal to the terminal disease stage (10–120 days). Among those miRNA changed in various age/gender/ muscle groups (miR-206, -1, -133a, -133b, -145, -21, -24), miR-206 was the only one consistently altered during the course of the disease pathology. In both sexes, mature miR-206 was increased in fast-twitch muscles preferably affected in the SOD1- G93A model, with highest expression towards the most severely affected animals. Importantly, miR-206 was also increased in the circulation of symptomatic animals and in a group of 12 definite ALS patients tested. We conclude that miR-206 is elevated in the circulation of symptomatic SOD1-G93A mice and possibly in human ALS patients. Although larger scale studies on ALS patients are warranted, miR-206 is a promising candidate biomarker for this motor neuron disease.
000057865 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/RYC-2011-08363$$9info:eu-repo/grantAgreement/ES/UZ/JIUZ-2012-IO-06
000057865 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000057865 590__ $$a3.234$$b2014
000057865 591__ $$aMULTIDISCIPLINARY SCIENCES$$b9 / 57 = 0.158$$c2014$$dQ1$$eT1
000057865 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000057865 700__ $$aManzano Martinez, Raquel
000057865 700__ $$0(orcid)0000-0003-0156-4230$$aOlivan Garcia, Sara$$uUniversidad de Zaragoza
000057865 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza Fernandez, Pilar$$uUniversidad de Zaragoza
000057865 700__ $$aGarcía-Redondo, Alberto
000057865 700__ $$0(orcid)0000-0001-5687-6704$$aOsta Pinzolas, Rosario$$uUniversidad de Zaragoza
000057865 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDepartamento de Anatomía, Embriología y Genética Animal$$cGenética
000057865 773__ $$g9, 2 (2014), e89065 [13 pp]$$pPLoS One$$tPLoS One$$x1932-6203
000057865 8564_ $$s385984$$uhttp://zaguan.unizar.es/record/57865/files/texto_completo.pdf$$yVersión publicada
000057865 8564_ $$s126865$$uhttp://zaguan.unizar.es/record/57865/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000057865 909CO $$ooai:zaguan.unizar.es:57865$$particulos$$pdriver
000057865 951__ $$a2017-06-20-14:56:51
000057865 980__ $$aARTICLE