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

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:

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).

Cite this article as:

Liew Hyunjeong, Kim Yun-Mi, Choi Soon Hee, Jang Ram Ah, Churchill David, Lee Hyung Sang and Suh Yoo-Hun, Soluble Neuregulin-1 from Microglia Enhances Amyloid Beta-induced Neuronal Death, CNS & Neurological Disorders - Drug Targets 2016; 15 (8) . https://dx.doi.org/10.2174/1871527315666160815160505