| First Author | Lee JK | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 29 | Pages | 12066-71 |
| PubMed ID | 23818595 | Mgi Jnum | J:198804 |
| Mgi Id | MGI:5499246 | Doi | 10.1073/pnas.1300894110 |
| Citation | Lee JK, et al. (2013) MST1 functions as a key modulator of neurodegeneration in a mouse model of ALS. Proc Natl Acad Sci U S A 110(29):12066-71 |
| abstractText | 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. |
