WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2160996
- author
- Li, Bei ; Zhong, Ling ; Yang, Xiangling ; Andersson, Tommy LU ; Huang, Min and Tang, Shao-Jun
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 6
- issue
- 8
- article number
- e22920
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000294121300008
- scopus:80051772933
- pmid:21857966
- 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
- 2016-04-01 13:01:56
- date last changed
- 2022-04-21 19:17:52
@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.}},
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 (PLoS)}},
series = {{PLoS ONE}},
title = {{WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity}},
url = {{https://lup.lub.lu.se/search/files/3117386/2254721.pdf}},
doi = {{10.1371/journal.pone.0022920}},
volume = {{6}},
year = {{2011}},
}