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WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity

Li, Bei; Zhong, Ling; Yang, Xiangling; Andersson, Tommy LU ; Huang, Min and Tang, Shao-Jun (2011) In PLoS ONE 6(8).
Abstract
Neurodegenration is a pathological hallmark of Alzheimer's disease (AD), but the underlying molecular mechanism remains elusive. Here, we present evidence that reveals a crucial role of Wnt5a signaling in this process. We showed that Wnt5a and its receptor Frizzled-5 (Fz5) were up-regulated in the AD mouse brain, and that beta-amyloid peptide (A beta), a major constituent of amyloid plaques, stimulated Wnt5a and Fz5 expression in primary cortical cultures; these observations indicate that Wnt5a signaling could be aberrantly activated during AD pathogenesis. In support of such a possibility, we observed that inhibition of Wnt5a signaling attenuated while activation of Wnt5a signaling enhanced A beta-evoked neurotoxicity, suggesting a role... (More)
Neurodegenration is a pathological hallmark of Alzheimer's disease (AD), but the underlying molecular mechanism remains elusive. Here, we present evidence that reveals a crucial role of Wnt5a signaling in this process. We showed that Wnt5a and its receptor Frizzled-5 (Fz5) were up-regulated in the AD mouse brain, and that beta-amyloid peptide (A beta), a major constituent of amyloid plaques, stimulated Wnt5a and Fz5 expression in primary cortical cultures; these observations indicate that Wnt5a signaling could be aberrantly activated during AD pathogenesis. In support of such a possibility, we observed that inhibition of Wnt5a signaling attenuated while activation of Wnt5a signaling enhanced A beta-evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related neurodegeneration. Furthermore, we also demonstrated that A beta-induced neurotoxicity depends on inflammatory processes, and that activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1 beta and TNF-alpha whereas inhibition of Wnt5a signaling attenuated the A beta-induced expression of the cytokines in cortical cultures. Our findings collectively suggest that aberrantly up-regulated Wnt5a signaling is a crucial pathological step that contributes to AD-related neurodegeneration by regulating neuroinflammation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
6
issue
8
publisher
Public Library of Science
external identifiers
  • wos:000294121300008
  • scopus:80051772933
ISSN
1932-6203
DOI
10.1371/journal.pone.0022920
language
English
LU publication?
yes
id
4e1b3fdd-1145-4c33-be2c-4877d376c87b (old id 2160996)
date added to LUP
2011-10-03 08:31:35
date last changed
2017-11-05 03:52:05
@article{4e1b3fdd-1145-4c33-be2c-4877d376c87b,
  abstract     = {Neurodegenration is a pathological hallmark of Alzheimer's disease (AD), but the underlying molecular mechanism remains elusive. Here, we present evidence that reveals a crucial role of Wnt5a signaling in this process. We showed that Wnt5a and its receptor Frizzled-5 (Fz5) were up-regulated in the AD mouse brain, and that beta-amyloid peptide (A beta), a major constituent of amyloid plaques, stimulated Wnt5a and Fz5 expression in primary cortical cultures; these observations indicate that Wnt5a signaling could be aberrantly activated during AD pathogenesis. In support of such a possibility, we observed that inhibition of Wnt5a signaling attenuated while activation of Wnt5a signaling enhanced A beta-evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related neurodegeneration. Furthermore, we also demonstrated that A beta-induced neurotoxicity depends on inflammatory processes, and that activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1 beta and TNF-alpha whereas inhibition of Wnt5a signaling attenuated the A beta-induced expression of the cytokines in cortical cultures. Our findings collectively suggest that aberrantly up-regulated Wnt5a signaling is a crucial pathological step that contributes to AD-related neurodegeneration by regulating neuroinflammation.},
  articleno    = {e22920},
  author       = {Li, Bei and Zhong, Ling and Yang, Xiangling and Andersson, Tommy and Huang, Min and Tang, Shao-Jun},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity},
  url          = {http://dx.doi.org/10.1371/journal.pone.0022920},
  volume       = {6},
  year         = {2011},
}