Title:Soluble Neuregulin-1 from Microglia Enhances Amyloid Beta-induced Neuronal Death
VOLUME: 15 ISSUE: 8
Author(s):Hyunjeong Liew, Yun-Mi Kim, Hee Soon Choi, Ah Ram Jang, David Churchill, Sang Hyung Lee and Yoo-Hun Suh
Affiliation:SMG-SNU Boramae medical center, Seoul, 156-707 South Korea., Neuroscience Research Institute, Gachon University, 774 Namdong-daero, Namdong-gu, Incheon, 21565, Korea.
Keywords:Amyloid beta peptide, ER stress, ErbB4, microglial cells, neuregulin-1, neuronal cell 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).
