کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2200994 | 1099990 | 2010 | 6 صفحه PDF | دانلود رایگان |
Recently, endoplasmic reticulum (ER) dysfunction has been implicated in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). Although up-regulation of caspase-12 has been reported in G93A SOD1 transgenic mice, it is controversial whether similar mechanisms operate in human FALS. We found that ER stress in cells stably expressing L84V SOD1 induces neuronal cell death and accelerates cleavage of caspase-4. We also detected oligomer formation of L84V SOD1 in L84V SOD1-expressing human neuroblastoma cells. These findings show that ER stress in L84V SOD1-expressing human cells causes the aggregation and inclusion bodies of L84V SOD1 to induce neuronal death through the accelerated cleavage of caspase-4.
Research highlights▶ ER dysfunction has been implicated in the pathogenesis of FALS. ▶ ER stress in cells with FALS mutation induces cell death and activation of caspase-4. ▶ We detected oligomer formation of the SOD1 in mutant SOD1-expressing cells. ▶ ER stress in cells with FALS mutation causes the aggregation of mutant SOD1.
Journal: Neurochemistry International - Volume 57, Issue 7, December 2010, Pages 838–843