Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 22, Issue 1, Pages 48-62Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2013.5803
Keywords
-
Funding
- FONDECYT [1120213]
- Center for Aging and Regeneration (CARE)
- Base Financing Program for Scientific and Technological Centers of Excellence
- CONICYT
- NIH National Center for Research Resources (NCRR)
- [PFB12/2007]
Ask authors/readers for more resources
Aims: To examine the role of the enzyme methionine sulfoxide reductase A-1 (MSRA-1) in amyloid-beta peptide (A beta)-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 A beta-peptide in muscle cells to prevent the reduction of oxidized methionines in proteins. In a constitutive transgenic A beta strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric A beta 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 A beta in vivo indirectly by dismantling the methionine sulfoxide repair system. The evidence presented here shows that the absence of MSRA-1 influences A beta 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 A beta-peptide aggregation and increments its deleterious effects in vivo. Antioxid. Redox Signal. 22, 48-62.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available