MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS
- MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS
- 류훈; 이재근; 신진희; 황상질; 곽병주; Ann C. Mckee; 이정희; Neil W. Kowall; 임대식; 최의주
- Issue Date
- Proceedings of the National Academy of Sciences of the United States of America
- VOL 110, NO 29-12071
- 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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