MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS
- Authors
- Lee, Jae Keun; Shin, Jin Hee; Hwang, Sang Gil; Gwag, Byoung Joo; McKee, Ann C.; Lee, Junghee; Kowall, Neil W.; Ryu, Hoon; Lim, Dae-Sik; Choi, Eui-Ju
- Issue Date
- 16-7월-2013
- Publisher
- NATL ACAD SCIENCES
- Keywords
- neurotoxicity; ROS
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.110, no.29, pp.12066 - 12071
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 110
- Number
- 29
- Start Page
- 12066
- End Page
- 12071
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/102696
- DOI
- 10.1073/pnas.1300894110
- ISSN
- 0027-8424
- Abstract
- 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.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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