57865 20201023135858.0 doi 10.1371/journal.pone.0089065 sideral 84847 ART-2014-84847 eng (orcid)0000-0002-7243-1737 Toivonen, Janne Markus Universidad de Zaragoza MicroRNA-206: A Potential Circulating Biomarker Candidate for Amyotrophic Lateral Sclerosis 2014 Access copy available to the general public Unrestricted Amyotrophic 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. info:eu-repo/grantAgreement/ES/MINECO/RYC-2011-08363 info:eu-repo/grantAgreement/ES/UZ/JIUZ-2012-IO-06 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.234 2014 MULTIDISCIPLINARY SCIENCES 9 / 57 = 0.158 2014 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0002-7477-8742 Manzano Martinez, Raquel (orcid)0000-0003-0156-4230 Olivan Garcia, Sara Universidad de Zaragoza (orcid)0000-0001-5740-0185 Zaragoza Fernandez, Pilar Universidad de Zaragoza García-Redondo, Alberto (orcid)0000-0001-5687-6704 Osta Pinzolas, Rosario Universidad de Zaragoza 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 9, 2 (2014), e89065 [13 pp] PLoS One PloS one 1932-6203 385984 http://zaguan.unizar.es/record/57865/files/texto_completo.pdf Versión publicada 126865 http://zaguan.unizar.es/record/57865/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:57865 articulos driver 2020-10-23-13:53:03 ARTICLE