2021Zagazig Journal of Pharmaceutical Sciences/Zagazig Journal of Pharmaceutical ScienceOpen access

Targeting wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway as a new therapeutic modality

Asmaa M. Abdelghafour, N. Younis, Sally K. Hammad, Hoda E. Mohamed

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Abstract

Wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway is an evolutionarily conserved signaling which is not only important for regulation of embryogenesis and organ development, but also for injury repair, homeostasis and tissue remodeling. Dysregulation of this pathway either by upregulation or even downregulation is highly implicated in various diseases such as; liver diseases, kidney diseases, lung fibrosis, heart failure, vascular calcification, osteoporosis, cellular senescence, neurodegeneration, Alzheimer's disease and cancers. Thus, targeting Wnt/β-catenin signaling has attracted scientific research as a good strategy ameliorating several diseases. In this review we discussed Wnt/β-catenin components, the Wnt-on state and the Wnt-off state. Furthermore, we summarized the effects of Wnt/β-catenin signaling in several distinct organs including brain, bone, liver, heart, lung and kidney. We also discussed various molecules that act as modulators of Wnt/β-catenin signaling pathway via targeting its components (Wnt, Frizzled, LRP5/6, Porcupine, Disheveled, β-catenin destruction complex and β-catenin activity) aiming to show their possible therapeutic potential in several diseases.

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Wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway is an evolutionarily conserved signaling which is not only important for regulation of embryogenesis and organ development, but also for injury repair, homeostasis and tissue remodeling. Dysregulation of this pathway either by upregulation or even downregulation is highly implicated in various diseases such as; liver diseases, kidney diseases, lung fibrosis, heart failure, vascular calcification, osteoporosis, cellular senescence, neurodegeneration, Alzheimer's disease and cancers. Thus, targeting Wnt/β-catenin signaling has attracted scientific research as a good strategy ameliorating several diseases. In this review we discussed Wnt/β-catenin components, the Wnt-on state and the Wnt-off state. Furthermore, we summarized the effects of Wnt/β-catenin signaling in several distinct organs including brain, bone, liver, heart, lung and kidney. We also discussed various molecules that act as modulators of Wnt/β-catenin signaling pathway via targeting its components (Wnt, Frizzled, LRP5/6, Porcupine, Disheveled, β-catenin destruction complex and β-catenin activity) aiming to show their possible therapeutic potential in several diseases.

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Available abstract

Wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway is an evolutionarily conserved signaling which is not only important for regulation of embryogenesis and organ development, but also for injury repair, homeostasis and tissue remodeling. Dysregulation of this pathway either by upregulation or even downregulation is highly implicated in various diseases such as; liver diseases, kidney diseases, lung fibrosis, heart failure, vascular calcification, osteoporosis, cellular senescence, neurodegeneration, Alzheimer's disease and cancers. Thus, targeting Wnt/β-catenin signaling has attracted scientific research as a good strategy ameliorating several diseases. In this review we discussed Wnt/β-catenin components, the Wnt-on state and the Wnt-off state. Furthermore, we summarized the effects of Wnt/β-catenin signaling in several distinct organs including brain, bone, liver, heart, lung and kidney. We also discussed various molecules that act as modulators of Wnt/β-catenin signaling pathway via targeting its components (Wnt, Frizzled, LRP5/6, Porcupine, Disheveled, β-catenin destruction complex and β-catenin activity) aiming to show their possible therapeutic potential in several diseases.

Key concepts: Wnt signaling pathway, LRP5, Frizzled, LRP6, Downregulation and upregulation, Beta-catenin, Cancer research, Biology

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