title: The protein oxidation repair enzyme methionine sulfoxide reductase a modulates Aβ aggregation and toxicity in vivo.
abstract: OBJECTIVE
  To examine the role of the enzyme methionine sulfoxide reductase A-1 (MSRA-1) in amyloid-β peptide (Aβ)-peptide aggregation and toxicity in vivo, using a Caenorhabditis elegans model of the human amyloidogenic disease inclusion body myositis.
  
  
  RESULTS
  MSRA-1 specifically reduces oxidized methionines in proteins. Therefore, a deletion of the msra-1 gene was introduced into transgenic C. elegans worms that express the Aβ-peptide in muscle cells to prevent the reduction of oxidized methionines in proteins. In a constitutive transgenic Aβ strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric Aβ species increases. These results correlate with enhanced synaptic dysfunction and mislocalization of the nicotinic acetylcholine receptor ACR-16 at the neuromuscular junction (NMJ).
  
  
  METHODS
  This approach aims at modulating the oxidation of Aβ in vivo indirectly by dismantling the methionine sulfoxide repair system. The evidence presented here shows that the absence of MSRA-1 influences Aβ aggregation and aggravates locomotor behavior and NMJ dysfunction. The results suggest that therapies which boost the activity of the Msr system could have a beneficial effect in managing amyloidogenic pathologies.
  
  
  CONCLUSIONS
  The absence of MSRA-1 modulates Aβ-peptide aggregation and increments its deleterious effects in vivo.
authors.affiliation: 1 Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile , Santiago, Chile .
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Minniti
authors.forename: Macarena S
authors.initials: MS
authors.lastname: Arrazola
authors.forename: Marcela
authors.initials: M
authors.lastname: Bravo-Zehnder
authors.forename: Francisca
authors.initials: F
authors.lastname: Ramos
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
authors.forename: Rebeca
authors.initials: R
authors.lastname: Aldunate
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D008124:Locomotion / Q000502:physiology; D008715:Methionine; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism*; D010084:Oxidation-Reduction; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D011978:Receptors, Nicotinic; C099378:acr-16 protein, C elegans; D008715:Methionine; D051150:Methionine Sulfoxide Reductases