title: Circulating microRNAs in Huntington's disease: Emerging mediators in metabolic impairment.
abstract: Huntington's disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40-45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni's correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient's organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington's Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression.
authors.affiliation: Department of Functional Biology, Physiology Area, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Díez-Planelles
authors.affiliation: Neurology Service, Hospital de Cabueñes, 33394 Gijón, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Lozano
authors.affiliation: Laboratory of Disorders of lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Crespo
authors.affiliation: Laboratory of Disorders of lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gil-Zamorano
authors.affiliation: Neurology Service, Asturias Central University Hospital, 33011 Oviedo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ribacoba
authors.affiliation: Renal, Vascular and Diabetes Research Laboratory, IIS-Jiménez Díaz Foundation, The Autonomous University of Madrid, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: González
authors.affiliation: Neurology Service, Asturias Central University Hospital, 33011 Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Suárez
authors.affiliation: Neurology Service, Jiménez Díaz Foundation University Hospital, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martínez-Descals
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Universidad Autónoma de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Martínez-Camblor
authors.affiliation: Molecular Genetics Service-Laboratory of Genetics, Asturias Central University Hospital, 33011 Oviedo, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Álvarez
authors.affiliation: Laboratory of Disorders of lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martín-Hernández
authors.affiliation: Department of Functional Biology, Physiology Area, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Huerta-Ruíz
authors.affiliation: Department of Functional Biology, Physiology Area, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: González-García
authors.affiliation: Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Cosgaya
authors.affiliation: Laboratory of Disorders of lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain; Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Visioli
authors.affiliation: Laboratory of Disorders of lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM+CSIC, 28049 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Dávalos
authors.affiliation: Department of Functional Biology, Physiology Area, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Iglesias-Gutiérrez
authors.affiliation: Department of Functional Biology, Physiology Area, Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain. Electronic address: tomascristina@uniovi.es.
authors.forename: C
authors.initials: C
authors.lastname: Tomás-Zapico
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D000074166:Circulating MicroRNA / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life
chemical_list: D015415:Biomarkers; D000074166:Circulating MicroRNA
keywords: Biomarker; Circulating microRNA; Huntington’s disease; Metabolism; Plasma; microRNA