| First Author | Prell T | Year | 2014 |
| Journal | J Neuroimmunol | Volume | 270 |
| Issue | 1-2 | Pages | 29-36 |
| PubMed ID | 24666819 | Mgi Jnum | J:355729 |
| Mgi Id | MGI:6872765 | Doi | 10.1016/j.jneuroim.2014.03.005 |
| Citation | Prell T, et al. (2014) Endoplasmic reticulum stress is accompanied by activation of NF-kappaB in amyotrophic lateral sclerosis. J Neuroimmunol 270(1-2):29-36 |
| abstractText | BACKGROUND: Recent studies have indicated that endoplasmic reticulum (ER) stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). ER stress occurs when the ER-mitochondria calcium cycle is disturbed and misfolded proteins accumulate in the ER. To cope with ER stress, cells activate the unfolded protein response (UPR). Accumulating evidence from non-neuronal cell models suggests that there is extensive cross-talk between the UPR and the NF-kappaB pathway. METHODS: Here we investigated the expression of NF-kappaB and the main UPR markers X-box binding protein 1 (XBP1), basic leucine-zipper transcription factor 6 (ATF6) and phosphorylated eukaryotic initiation factor-2alpha (p-eIF2) in mutated SOD1(G93A) cell models of ALS, as well as their modulation by lipopolysaccharide and ER-stressing (tunicamycin) stimuli. RESULTS: Expression of NF-kappaB was enhanced in the presence of SOD1(G93A). Lipopolysaccharide did not induce the UPR in NSC34 cells and motor neurons in a mixed motor neuron-glia coculture system. The induction of the UPR by tunicamycin was accompanied by activation of NF-kappaB in NSC34 cells and motor neurons. CONCLUSION: Our data linked two important pathogenic mechanisms of ALS, ER stress and NF-kappaB signalling, in motor neurons. |
