G-protein-coupled inwardly rectifying potassium (GIRK) channel activation by the p75 neurotrophin receptor is required for amyloid beta toxicity

May, Linda M., Anggono, Victor, Gooch, Helen M., Jang, Se E., Matusica, Dusan, Kerbler, Georg M., Meunier, Frederic A., Sah, Pankaj and Coulson, Elizabeth J. (2017) G-protein-coupled inwardly rectifying potassium (GIRK) channel activation by the p75 neurotrophin receptor is required for amyloid beta toxicity. Frontiers in Neuroscience, 11 455: . doi:10.3389/fnins.2017.00455


Author May, Linda M.
Anggono, Victor
Gooch, Helen M.
Jang, Se E.
Matusica, Dusan
Kerbler, Georg M.
Meunier, Frederic A.
Sah, Pankaj
Coulson, Elizabeth J.
Title G-protein-coupled inwardly rectifying potassium (GIRK) channel activation by the p75 neurotrophin receptor is required for amyloid beta toxicity
Journal name Frontiers in Neuroscience   Check publisher's open access policy
ISSN 1662-453X
Publication date 2017-08-08
Year available 2017
Sub-type Article (original research)
DOI 10.3389/fnins.2017.00455
Open Access Status DOI
Volume 11
Issue 455
Total pages 14
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Language eng
Formatted abstract
Alzheimer's disease is characterized by cognitive decline, neuronal degeneration, and the accumulation of amyloid-beta (Aβ). Although, the neurotoxic Aβ peptide is widely believed to trigger neuronal dysfunction and degeneration in Alzheimer's disease, the mechanism by which this occurs is poorly defined. Here we describe a novel, Aβ-triggered apoptotic pathway in which Aβ treatment leads to the upregulation of G-protein activated inwardly rectifying potassium (GIRK/Kir3) channels, causing potassium efflux from neurons and Aβ-mediated apoptosis. Although, GIRK channel activity is required for Aβ-induced neuronal degeneration, we show that it is not sufficient, with coincident signaling by the p75 neurotrophin receptor (p75NTR) also required for potassium efflux and cell death. Our results identify a novel role for GIRK channels in mediating apoptosis, and provide a previously missing mechanistic link between the excitotoxicity of Aβ and its ability to trigger cell death pathways, such as that mediated by p75NTR. We propose that this death-signaling pathway contributes to the dysfunction of neurons in Alzheimer's disease and is responsible for their eventual degeneration.
Keyword p75NTR
Amyloid β
Alzheimer’s disease
Neurodegeneration
Excitotoxicity
Potassium flux
Kir3
GIRK channel
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Faculty of Medicine
School of Biomedical Sciences Publications
 
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Created: Wed, 09 Aug 2017, 10:38:38 EST by Victor Anggono on behalf of Clem Jones Centre for Ageing Dementia Research