title: Quantitative analysis of proteins of metabolism by reverse phase protein microarrays identifies potential biomarkers of rare neuromuscular diseases.
abstract: BACKGROUND
  Muscle diseases have been associated with changes in the expression of proteins involved in energy metabolism. To this aim we have developed a number of monoclonal antibodies against proteins of energy metabolism.
  
  
  METHODS
  Herein, we have used Reverse Phase Protein Microarrays (RPMA), a high throughput technique, to investigate quantitative changes in protein expression with the aim of identifying potential biomarkers in rare neuromuscular diseases. A cohort of 73 muscle biopsies that included samples from patients diagnosed of Duchenne (DMD), Becker (BMD), symptomatic forms of DMD and BMD in female carriers (Xp21 Carriers), Limb Girdle Muscular Dystrophy Type 2C (LGMD2C), neuronal ceroid lipofuscinosis (NCL), glycogenosis type V (Mc Ardle disease), isolated mitochondrial complex I deficiency, intensive care unit myopathy and control donors were investigated. The nineteen proteins of energy metabolism studied included members of the mitochondrial oxidation of pyruvate, the tricarboxylic acid cycle, β-oxidation of fatty acids, electron transport and oxidative phosphorylation, glycogen metabolism, glycolysis and oxidative stress using highly specific antibodies.
  
  
  RESULTS
  The results indicate that the phenotype of energy metabolism offers potential biomarkers that could be implemented to refine the understanding of the biological principles of rare diseases and, eventually, the management of these patients.
  
  
  CONCLUSIONS
  We suggest that some biomarkers of energy metabolism could be translated into the clinics to contribute to the improvement of the clinical handling of patients affected by rare diseases.
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular, c/ Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049, Madrid, Spain. fsantacatterina@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. fsantacatterina@cbm.csic.es.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. fsantacatterina@cbm.csic.es.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Santacatterina
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular, c/ Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049, Madrid, Spain. mchamorro@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. mchamorro@cbm.csic.es.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. mchamorro@cbm.csic.es.
authors.forename: Margarita
authors.initials: M
authors.lastname: Chamorro
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular, c/ Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049, Madrid, Spain. cnunez@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. cnunez@cbm.csic.es.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. cnunez@cbm.csic.es.
authors.forename: Cristina Núñez
authors.initials: CN
authors.lastname: de Arenas
authors.affiliation: Instituto de Investigación Biomédico de Vigo (IBIV), Hospital Universitario de Vigo, Meixoeiro, 36200, Vigo, Spain. carmen.navarro.fernandez.balbuena@sergas.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. mamcasanueva.h12o@gmail.com.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. mamcasanueva.h12o@gmail.com.|Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain. mamcasanueva.h12o@gmail.com.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular, c/ Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049, Madrid, Spain. jmcuezva@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. jmcuezva@cbm.csic.es.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. jmcuezva@cbm.csic.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Cuezva
authors.affiliation: Departamento de Biología Molecular, Centro de Biología Molecular, c/ Nicolás Cabrera 1, Universidad Autónoma de Madrid, 28049, Madrid, Spain. msanchez@cbm.csic.es.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. msanchez@cbm.csic.es.|Instituto de Investigación Hospital 12 de Octubre, ISCIII, Madrid, Spain. msanchez@cbm.csic.es.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Aragó
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000473:pathology; D009468:Neuromuscular Diseases / Q000175:diagnosis / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D035583:Rare Diseases / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000906:Antibodies; D015415:Biomarkers