Decreased upstream survival signal and accentuated apoptotic signal to oxidative stress could be important factors of motor neuron death mechanism in vitro model of familial ALS

Abstract

Numerous studies about the role of SOD1 mutant gene in familial ALS(fALS) have shown abundant new information on possible pathogenic mechanisms of fALS and sporadic ALS. Despite the numerous studies using in vitro model of fALS, alterations of upstream cell survival signals have not been evaluated. This study was conducted to investigate the effect of oxidative stress (H2O2) on the cell survival signals pathway of G93A mutated 4.1 VSC motoneuron cell lines, in vitro model of familial ALS. These results show that G93A point-mutated type is more vulnerable to oxidative stress than wild type, and this vulnerability is related with not only increased signal of downstream apoptotic pathway, but also decreased cell survival signals. such as PI3K/Akt. Therefore, it is suggested that modulation of these enzymes could be a new potential therapeutic strategy for motor neuron diseases associated with oxidative injury.