期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 22, 期 1, 页码 48-62出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2013.5803
关键词
-
资金
- 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]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据