Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine,RSC Chemical Biology

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Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2021-06-01 , DOI: 10.1039/d1cb00063b
Clémence Bonnet _{1,

2} , Anvi Brahmbhatt ₁ , Sophie X Deng _{1,

3} , Jie J Zheng _{1,

3}

Affiliation

Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration and remodeling in adults. While aberrant Wnt signaling contributes to diseases such as cancer, activation of Wnt/β-catenin signaling is a target of interest in stem cell therapy and regenerative medicine. Recent high throughput screenings from chemical and biological libraries, combined with improved gene expression reporter assays of Wnt/β-catenin activation together with rational drug design, led to the development of a myriad of Wnt activators, with different mechanisms of actions. Among them, Wnt mimics, antibodies targeting Wnt inhibitors, glycogen-synthase-3β inhibitors, and indirubins and other natural product derivatives are emerging modalities to treat bone, neurodegenerative, eye, and metabolic disorders, as well as prevent ageing. Nevertheless, the creation of Wnt-based therapies has been hampered by challenges in developing potent and selective Wnt activators without off-target effects, such as oncogenesis. On the other hand, to avoid these risks, their use to promote ex vivo expansion during tissue engineering is a promising application.

中文翻译：

Wnt信号激活：干细胞治疗和再生医学的靶点和治疗机会

Wnt 蛋白是分泌型形态发生素，在成人胚胎发育、干细胞增殖、自我更新、组织再生和重塑中发挥关键作用。虽然异常的 Wnt 信号传导会导致癌症等疾病，但 Wnt/β-catenin 信号传导的激活是干细胞治疗和再生医学感兴趣的目标。最近从化学和生物文库中进行的高通量筛选，结合改进的 Wnt/β-连环蛋白激活基因表达报告基因分析以及合理的药物设计，导致了多种具有不同作用机制的 Wnt 激活剂的开发。其中，Wnt 模拟物、针对 Wnt 抑制剂的抗体、糖原合成酶 3β 抑制剂以及靛玉红和其他天然产物衍生物是治疗骨骼、神经退行性疾病、眼睛和代谢疾病以及预防衰老的新兴方法。然而，基于 Wnt 的疗法的创建一直受到开发有效且选择性的 Wnt 激活剂而没有脱靶效应（例如肿瘤发生）方面的挑战的阻碍。另一方面，为了避免这些风险，在组织工程过程中使用它们来促进离体扩增是一个有前景的应用。

更新日期：2021-06-24

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