| First Author | Li B | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 8 | Pages | e22920 |
| PubMed ID | 21857966 | Mgi Jnum | J:176368 |
| Mgi Id | MGI:5291547 | Doi | 10.1371/journal.pone.0022920 |
| Citation | Li B, et al. (2011) WNT5A signaling contributes to Abeta-induced neuroinflammation and neurotoxicity. PLoS One 6(8):e22920 |
| abstractText | 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 (Abeta), 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 Abeta-evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related neurodegeneration. Furthermore, we also demonstrated that Abeta-induced neurotoxicity depends on inflammatory processes, and that activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1beta and TNF-alpha whereas inhibition of Wnt5a signaling attenuated the Abeta-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. |
