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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure. To develop effective treatments for this devastating disease, an appropriate strategy for targeting the molecule responsible for the pathogenesis of ALS is needed. We previously reported that mutant SOD1 protein causes motor neuron death through activation of ASK1, a mitogen-activated protein kinase kinase kinase. Additionally, we recently developed K811 and K812, which are selective inhibitors for ASK1. Here, we report the effect of K811 and K812 in a mouse model of ALS (SOD1(G93A) transgenic mice). Oral administration of K811 or K812 significantly extended the life span of SOD1(G93A) transgenic mice (1.06 and 1.08% improvement in survival). Moreover, ASK1 activation observed in the lumbar spinal cord of mice at the disease progression stage was markedly decreased in the K811- and K812-treated groups. In parallel, immunohistochemical analysis revealed that K811 and K812 treatment inhibited glial activation in the lumbar spinal cord of SOD1(G93A) transgenic mice. These results reinforce the importance of ASK1 as a therapeutic target for ALS treatment.

Chub mackerel Scomber japonicus and spotted mackerel S. australasicus are important fishery resources in the countries adjacent to the East China Sea (ECS). During February to March in 2004 and 2005, based on species identification using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of mtDNA, we examined the larval distribution, transport and growth of both species in the southern ECS, where extremely high abundances of Scomber spp. larvae are found. Distribution of S. australasicus was in a more southern area than was S. japonicus, with a higher and narrower range of habitat temperature (20 to 23°C versus 15 to 22°C), although there was some spatial overlap. In 2004, when an intrusion of the warm Kuroshio Branch Current north of Taiwan was evident, S. australasicus were transported northeastward, while they dispersed eastward along the Kuroshio front in 2005 when the intrusion was weak. Although S. japonicus showed a similar pattern of transport and dispersal to S. australasicus, it was more gradual, corresponding with the weaker flow in the northern part of the study area. The daily specific growth rates of S. japonicus and S. australasicus were 6.2 to 8.2% and 7.7 to 9.3% of body length per day, respectively, and growth was significantly higher in 2004 than in 2005 for both species, with both habitat temperature and food availability being higher in 2004. Our study provides fundamental information on the spawning and recruitment of these 2 mackerel species on which to base predictive models, which are essential for protecting these shared stocks that migrate across the boundaries within the ECS.