Reference - Detail
| 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 | 7.04 |
| Times Cited | 11 |
| WOS Category | ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| C.elegans | tm1421 |