| First Author | Prell T | Year | 2012 |
| Journal | Eur J Neurosci | Volume | 35 |
| Issue | 5 | Pages | 652-60 |
| PubMed ID | 22390177 | Mgi Jnum | J:184476 |
| Mgi Id | MGI:5424082 | Doi | 10.1111/j.1460-9568.2012.08008.x |
| Citation | Prell T, et al. (2012) The unfolded protein response in models of human mutant G93A amyotrophic lateral sclerosis. Eur J Neurosci 35(5):652-60 |
| abstractText | Recent studies indicate that endoplasmic reticulum (ER) stress is involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). ER stress occurs when the ER-mitochondria calcium cycle (ERMCC) is disturbed and misfolded proteins accumulate in the ER. To cope with ER stress, the cell engages the unfolded protein response (UPR). While activation of the UPR has been shown in some ALS models and tissues, ER stress elements have not been studied directly in motor neurons. Here we investigated the expression of XBP1 and ATF6alpha and phosphorylation of eIF2alpha, and their modulation, in mutated SOD1(G93A) NSC34 and animal model of ALS. Expression of XBP1 and ATF6alpha mRNA and protein was enhanced in SOD1(G93A) NSC34 cells. Activation of ATF6alpha and XBP1 and phosphorylation of eIF2alpha were detectable in mutated SOD1(G93A) motor but not in wild-type motor neurons. Treatment with the ER stressor thapsigargin enhanced phosphorylation of eIF2alpha and activated proteolysis of ATF6alpha and splicing of XBP1 in NSC34 and motor neurons in a time-dependent manner. The present study thus provides direct evidence of activated UPR in motor neurons which overexpress human pathogenic mutant SOD1(G93A) , providing evidence that ER stress plays a major role in ALS. |
