X-Linked inhibitor of apoptosis protein is involved in mutant SOD1-mediated neuronal degeneration.

摘要: Mutations in the superoxide dismutase 1 (SOD1) gene cause degeneration of motor neurons familial amyotrophic lateral sclerosis (FALS). An apoptotic process including caspase-1 and -3 has been shown to participate pathogenesis FALS transgenic (Tg) mouse model. Here we report that IAP proteins, potent inhibitors apoptosis, are involved Tg pathologic process. The levels X-linked inhibitor apoptosis protein (XIAP) mRNA were significantly decreased spinal cord symptomatic G93A-SOD1 mice compared with littermates. In contrast, cIAP-1 increased mice, whereas cIAP-2 unchanged. situ hybridization showed expression XIAP was remarkably reduced strongly reactive astrocytes mice. Overexpression markedly inhibited cell death caspase-3 activity neuro2a cells expressing mutant SOD1. Deletional analysis revealed N-terminal domain XIAP, BIR1-2 domains, essential for this inhibitory activity. These results suggest plays a role mechanism progression disease SOD1 holds therapeutic possibilities FALS.