title: Soluble Neuregulin-1 from Microglia Enhances Amyloid Beta-induced Neuronal Death.
abstract: Neuregulin-1 (NRG-1) is a ligand of the epidermal growth factor receptor (erbB), and its interaction involves activation of the glutamatergic N-methyl-Daspartate receptor, which increases the expression of the β2 subunit of the γ- aminobutyric acid receptor and subunits of the nicotinic acetylcholine receptor. In the dentate gyrus of 14-month-old Tg2576 mice, NRG-1 was strongly expressed compared with age-matched controls. The supernatant of oligomeric amyloid β peptide (Aβ42)-treated glial cells enhanced the Aβ42;-induced cytotoxic effects, but the expression of Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand in microglial cells was not changed upon cytotoxic treatment. This suggests that the oligomeric form of Aβ42 toxicity is not related to apoptosis, which is mediated by cell-to-cell interaction. During the 24-h incubation, the secretion of the soluble form of NRG-1 was increased, but interleukin 6 secretion was not changed. Further, soluble NRG-1 increased Aβ42-induced toxicity. In conclusion, soluble NRG-1 significantly enhanced oligomeric Aβ42-induced toxicity through the activation of endoplasmic reticulum stress by the increase of a phospho-translation initiation factor 2 alpha (p-eIF2α).
authors: Hyunjeong
authors: H
authors: Liew
authors: Yun-Mi
authors: YM
authors: Kim
authors: Hee Soon
authors: HS
authors: Choi
authors: Ah Ram
authors: AR
authors: Jang
authors: David
authors: D
authors: Churchill
authors: SMG-SNU Boramae medical center, Seoul, 156-707 South Korea. nslee@snu.ac.kr.
authors: Sang Hyung
authors: SH
authors: Lee
authors: Neuroscience Research Institute, Gachon University, 774 Namdong-daero, Namdong-gu, Incheon, 21565, Korea. yhsuh@snu.ac.kr.
authors: Yoo-Hun
authors: YH
authors: Suh
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000737:chemistry* / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053222:Fas Ligand Protein; D020890:Neuregulin-1; D010446:Peptide Fragments; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand; C075222:amyloid beta-protein (1-42)