Glutathione peroxidase activity is neuroprotective in models of Huntington's disease.
Glutathione peroxidase activity is neuroprotective in models of Huntington's disease.
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DOI：
10.1038/ng.2732
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发表时间：
2013-10
期刊：
影响因子：
30.8
通讯作者：
Giorgini, Flaviano
中科院分区：
文献类型：
--
作者：
Mason, Robert P.;Casu, Massimiliano;Butler, Nicola;Breda, Carlo;Campesan, Susanna;Clapp, Jannine;Green, Edward W.;Dhulkhed, Devyani;Kyriacou, Charalambos P.;Giorgini, Flaviano
Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion encoding a polyglutamine tract in the huntingtin (htt) protein. Here, we report a genome-wide overexpression suppressor screen which identified 317 open reading frames that ameliorate toxicity of a mutant htt fragment in yeast, and play roles in diverse cellular processes, including mitochondrial import and copper metabolism. Two suppressors encode glutathione peroxidases (GPxs), conserved antioxidant enzymes that reduce hydrogen peroxide and lipid hydroperoxides. Using genetic and pharmacological approaches in yeast, mammalian cells and Drosophila, we find that GPx activity robustly ameliorates HD-relevant metrics and is more protective than other antioxidant approaches tested. Importantly, we observe that GPx activity – unlike many antioxidant treatments – does not inhibit autophagy, an important mechanism for clearing mutant htt. As previous clinical trials indicate GPx mimetics are well-tolerated in humans, this study may have important implications for the treatment of HD.
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影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
11
作者：
Allebrandt, K. V.;Amin, N.;Roenneberg, T.
通讯作者：
Roenneberg, T.
DOI：
10.1083/jcb.200112104
发表时间：
2002-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Meriin AB;Zhang X;He X;Newnam GP;Chernoff YO;Sherman MY
通讯作者：
Sherman MY
DOI：
10.1073/pnas.2628045100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Apostol, BL;Kazantsev, A;Thompson, LM
通讯作者：
Thompson, LM
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.