Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal

Tang, Sung-Chun, Lathia, Justin D., Selvaraj, Pradeep K., Jo, Dong-Gyu, Mughal, Mohamed R., Cheng, Aiwu, Siler, Dominic A., Markesbery, William R., Arumugam, Thiruma V. and Mattson, Mark P. (2008) Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Experimental Neurology, 213 1: 114-121. doi:10.1016/j.expneurol.2008.05.014


Author Tang, Sung-Chun
Lathia, Justin D.
Selvaraj, Pradeep K.
Jo, Dong-Gyu
Mughal, Mohamed R.
Cheng, Aiwu
Siler, Dominic A.
Markesbery, William R.
Arumugam, Thiruma V.
Mattson, Mark P.
Title Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal
Formatted title
Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid β-peptide and the membrane lipid peroxidation product 4-hydroxynonenal
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 0014-4886
1090-2430
Publication date 2008-09
Sub-type Article (original research)
DOI 10.1016/j.expneurol.2008.05.014
Volume 213
Issue 1
Start page 114
End page 121
Total pages 8
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Abstract The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We recently found that neurons express several TLRs, and that the levels of TLR2 and TLR4 are increased in neurons in response to energy deprivation. Here we report that TLR4 expression increases in neurons when exposed to amyloid β-peptide (Aβ1–42) or the lipid peroxidation product 4-hydroxynonenal (HNE). Neuronal apoptosis triggered by Aβ and HNE was mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibited reduced JNK and caspase-3 activation and were protected against apoptosis induced by Aβ and HNE. Levels of TLR4 were decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched control subjects, possibly as the result of loss of neurons expressing TLR4. Our findings suggest that TLR4 signaling increases the vulnerability of neurons to Aβ and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD.
Keyword Toll-like receptors
Amyloid beta-peptide
4-hydroxynonenal
Neuron
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 12:22:34 EST