The protein oxidation repair enzyme methionine sulfoxide reductase a modulates A? aggregation and toxicity in vivo.

ABSTRACT: To examine the role of the enzyme methionine sulfoxide reductase A-1 (MSRA-1) in amyloid-? peptide (A?)-peptide aggregation and toxicity in vivo, using a Caenorhabditis elegans model of the human amyloidogenic disease inclusion body myositis.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 A?-peptide in muscle cells to prevent the reduction of oxidized methionines in proteins. In a constitutive transgenic A? strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric A? species increases. These results correlate with enhanced synaptic dysfunction and mislocalization of the nicotinic acetylcholine receptor ACR-16 at the neuromuscular junction (NMJ).This approach aims at modulating the oxidation of A? in vivo indirectly by dismantling the methionine sulfoxide repair system. The evidence presented here shows that the absence of MSRA-1 influences A? 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.The absence of MSRA-1 modulates A?-peptide aggregation and increments its deleterious effects in vivo.

SUBMITTER: Minniti AN 

PROVIDER: S-EPMC4270145 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature