Soluble Neuregulin-1 from Microglia Enhances Amyloid Beta-induced Neuronal Death

Author(s): Hyunjeong Liew, Yun-Mi Kim, Hee Soon Choi, Ah Ram Jang, David Churchill, Sang Hyung Lee, Yoo-Hun Suh.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 15 , Issue 8 , 2016

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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).

Keywords: Amyloid beta peptide, ER stress, ErbB4, microglial cells, neuregulin-1, neuronal cell death.

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Article Details

VOLUME: 15
ISSUE: 8
Year: 2016
Page: [918 - 926]
Pages: 9
DOI: 10.2174/1871527315666160815160505
Price: $58

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