AUTHOR=Lee Jae Keun , Hwang Sang Gil , Shin Jin Hee , Shim Jaekyung , Choi Eui-Ju 

TITLE=CIIA prevents SOD1(G93A)-induced cytotoxicity by blocking ASK1-mediated signaling

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 8 - 2014

YEAR=2014

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00179

DOI=10.3389/fncel.2014.00179

ISSN=1662-5102

ABSTRACT=<p>Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with higher selectivity in degeneration of motor neurons. However, the molecular mechanism by which the ALS-linked mutants of human superoxide dismutase 1 (SOD1) gene induce neurotoxicity remains obscure yet. Here, we show that depletion of CIIA expression by RNA interference (RNAi) promoted cytotoxicity caused by ALS-linked G93A mutant of the SOD1 gene. The RNAi-mediated knockdown of CIIA also enhanced the SOD1(G93A)-induced interaction between ASK1 and TRAF2 as well as ASK1 activity. Furthermore, endogenous silencing of CIIA by RNAi augmented the effects of SOD1(G93A) on reduction of mitochondria membrane potential (Δψ<sub>m</sub>), release of cytochrome c into the cytoplasm, and caspase activation. Together, our results suggest that CIIA negatively modulates ASK1-mediated cytotoxic signaling processes in a SOD1(G93A)-expressing cellular model of ALS.</p>