Endoplasmic reticulum stress is accompanied by activation of NF-κB in amyotrophic lateral sclerosis

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-κB pathway. Methods Here we investigated the expression of NF-κB and the main UPR markers X-box binding protein 1 (XBP1), basic leucine-zipper transcription factor 6 (ATF6) and phosphorylated eukaryotic initiation factor-2α (p-eIF2) in mutated SOD1G93A cell models of ALS, as well as their modulation by lipopolysaccharide and ER-stressing (tunicamycin) stimuli. Results Expression of NF-κB was enhanced in the presence of SOD1G93A. 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-κB in NSC34 cells and motor neurons. Conclusion Our data linked two important pathogenic mechanisms of ALS, ER stress and NF-κB signalling, in motor neurons.