title: Endoplasmic reticulum stress is accompanied by activation of NF-κB in amyotrophic lateral sclerosis.
abstract: 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 SOD1(G93A) 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 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-κB in NSC34 cells and motor neurons.
  
  
  CONCLUSIONS
  Our data linked two important pathogenic mechanisms of ALS, ER stress and NF-κB signalling, in motor neurons.
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany. Electronic address: tino.prell@med.uni-jena.de.
authors.forename: T
authors.initials: T
authors.lastname: Prell
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lautenschläger
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Weidemann
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ruhmer
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: O W
authors.initials: OW
authors.lastname: Witte
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Grosskreutz
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D016328:NF-kappa B; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Endoplasmic reticulum stress; Motor neuron; NFkB; Superoxide dismutase; Unfolded protein response