WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity

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

Research output: Contribution to journalArticlepeer-review

57 Citations (SciVal)
96 Downloads (Pure)

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.
Original languageEnglish
Article numbere22920
JournalPLoS ONE
Volume6
Issue number8
DOIs
Publication statusPublished - 2011

Subject classification (UKÄ)

  • Cancer and Oncology

Fingerprint

Dive into the research topics of 'WNT5A Signaling Contributes to A beta-Induced Neuroinflammation and Neurotoxicity'. Together they form a unique fingerprint.

Cite this