Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 12, Issue -, Pages 448-457Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/2074
Keywords
disease; Wnt; Wnt signaling; beta-catenin; Wnt/Ca; frizzled; Fzd; sFRPs; Dickkopf; DKK; LRP; RNAi; blocking antibodies; translational research; therapy; treatment; therapeutic strategies; review
Categories
Funding
- NIAMS NIH HHS [T32 AR056969-02, 2T32 AR07019, T32 AR007019] Funding Source: Medline
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The body of scientific literature linking Wnts and Wnt-associated proteins to human disease processes continues to grow in parallel with new discoveries from basic science laboratories that further characterize the elaborate cellular events following the binding of Wnts to their receptors. While Wnt-mediated signaling has long been known to play a major role in human carcinogenesis, accumulating evidence indicates that Wnts are also important mediators of inflammation and recovery from injury. The binding of secreted Wnt ligands to their receptors offers an attractive and accessible target for therapeutic regulation of these signaling pathways. Several promising preliminary studies have already addressed potential avenues for the manipulation of Wnt signaling in disease processes. This review will focus on disease processes involving the regulation of Wnt signaling at the level of Wnt binding to its target receptors. Wnt proteins, Wnt receptors, and secreted Wnt inhibitors are attractive as potential therapeutic agents and targets due to their extracellular location. In addition, since Wnt signaling results in a diverse array of downstream intracellular events, many of which are not fully understood, the targeting of this pathway at the most upstream site of pathway activation also provides a strategic advantage for therapy. As the list of Wnt-related diseases continues to grow, advances in our understanding of the biochemical and molecular mechanisms underlying Wnt signaling may ultimately translate into innovative ways to treat Wnt-related disease processes in patients.
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