RRC ID 45808
Author Minniti AN, Arrazola MS, Bravo-Zehnder M, Ramos F, Inestrosa NC, Aldunate R.
Title The protein oxidation repair enzyme methionine sulfoxide reductase a modulates Aβ aggregation and toxicity in vivo.
Journal Antioxid Redox Signal
Abstract AIMS: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).
INNOVATION: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.
CONCLUSION:The absence of MSRA-1 modulates Aβ-peptide aggregation and increments its deleterious effects in vivo.
Volume 22(1)
Pages 48-62
Published 2015-1-1
DOI 10.1089/ars.2013.5803
PMID 24988428
PMC PMC4270145
MeSH Amyloid beta-Peptides / metabolism Animals Animals, Genetically Modified Blotting, Western Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism Immunoprecipitation Locomotion / physiology Methionine Methionine Sulfoxide Reductases / metabolism* Oxidation-Reduction Receptors, Nicotinic / metabolism
IF 5.828
Times Cited 11
C.elegans tm1421