WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity

Bei Li, Ling Zhong, Xiangling Yang, Tommy Andersson, Min Huang, Shao-Jun Tang

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 (Aβ), 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 Aβ-evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related neurodegeneration. Furthermore, we also demonstrated that Aβ-induced neurotoxicity depends on inflammatory processes, and that activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1β and TNF-α whereas inhibition of Wnt5a signaling attenuated the Aβ-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.

Original languageEnglish (US)
Article numbere22920
JournalPLoS One
Volume6
Issue number8
DOIs
StatePublished - 2011

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neurotoxicity
Alzheimer disease
Alzheimer Disease
amyloid
cytokines
Frizzled Receptors
Cytokines
Amyloid Plaques
interleukin-1
Interleukin-1
Amyloid
Chemical activation
pathogenesis
peptides
brain
receptors
mice
Brain

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. / Li, Bei; Zhong, Ling; Yang, Xiangling; Andersson, Tommy; Huang, Min; Tang, Shao-Jun.

In: PLoS One, Vol. 6, No. 8, e22920, 2011.

Research output: Contribution to journalArticle

Li, Bei ; Zhong, Ling ; Yang, Xiangling ; Andersson, Tommy ; Huang, Min ; Tang, Shao-Jun. / WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. In: PLoS One. 2011 ; Vol. 6, No. 8.
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