MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS
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- Jae Keun Lee
- Laboratory of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea;
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- Jin Hee Shin
- GNT Pharma, Suwon 446-906, Korea;
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- Sang Gil Hwang
- Laboratory of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea;
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- Byoung Joo Gwag
- GNT Pharma, Suwon 446-906, Korea;
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- Ann C. McKee
- Department of Neurology and Pathology, Boston University School of Medicine and VA Boston Healthcare System, Boston, MA 02130;
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- Junghee Lee
- Department of Neurology and Pathology, Boston University School of Medicine and VA Boston Healthcare System, Boston, MA 02130;
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- Neil W. Kowall
- Department of Neurology and Pathology, Boston University School of Medicine and VA Boston Healthcare System, Boston, MA 02130;
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- Hoon Ryu
- Department of Neurology and Pathology, Boston University School of Medicine and VA Boston Healthcare System, Boston, MA 02130;
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- Dae-Sik Lim
- Department of Biological Sciences, Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejon 305-701, Korea; and
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- Eui-Ju Choi
- Laboratory of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea;
書誌事項
- 公開日
- 2013-07
- DOI
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- 10.1073/pnas.1300894110
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Dominant mutations in the gene for superoxide dismutase 1 (SOD1) give rise to familial ALS by an unknown mechanism. Here we show that genetic deficiency of mammalian sterile 20-like kinase 1 (MST1) delays disease onset and extends survival in mice expressing the ALS-associated G93A mutant of human SOD1. SOD1(G93A) induces dissociation of MST1 from a redox protein thioredoxin-1 and promotes MST1 activation in spinal cord neurons in a reactive oxygen species–dependent manner. Moreover, MST1 was found to mediate SOD1(G93A)-induced activation of p38 mitogen-activated protein kinase and caspases as well as impairment of autophagy in spinal cord motoneurons of SOD1(G93A) mice. Our findings implicate MST1 as a key determinant of neurodegeneration in ALS.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (29), 12066-12071, 2013-07
Proceedings of the National Academy of Sciences