The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates A beta Aggregation and Toxicity In Vivo

Minniti A.N.; Arrázola M.S.; Bravo-Zehnder, M; Ramos, F; Inestrosa, N. C.; Aldunate, R

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. Antioxid. Redox Signal. 22, 48-62.

Más información

Título según WOS: The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates A beta Aggregation and Toxicity In Vivo
Título según SCOPUS: The protein oxidation repair enzyme methionine sulfoxide reductase A modulates A? aggregation and toxicity in vivo
Título de la Revista: ANTIOXIDANTS AND REDOX SIGNALING
Volumen: 22
Número: 1
Editorial: Mary Ann Liebert Inc.
Fecha de publicación: 2015
Página de inicio: 48
Página final: 62
Idioma: English
DOI:

10.1089/ars.2013.5803

Notas: ISI, SCOPUS - ISI