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Domestication of chemicals attacking metazoan embryogenesis: identification of safe natural products modifying developmental signaling pathways in human
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2021-08-11 , DOI: 10.1038/s41429-021-00461-y
Naoyuki Nishiya 1 , Honami Yonezawa 1
Affiliation  

Soil microorganisms are rich sources of bioactive natural products. Interspecies interactions are the cues of their production and refine biological activities. These interactions in natural environments include the interplay between microorganisms and Metazoans (animals), such as nematodes, insects, and ticks. Chemical intercellular communication modulators could exert ideal Metazoan-selective toxicity for defending microorganisms. Developmental signaling pathways, such as the Notch, TGF-beta, and Wnt pathways, are intercellular communication networks that contribute to the reproducible formation of complex higher-order Metazoan body structures. Natural modifiers of the developmental signaling pathway are attractive therapeutic seeds for carcinoma and sarcoma treatment. However, these fundamental signaling pathways also play indispensable physiological roles and their perturbation could lead to toxicity, such as defects in stem cell physiology and tissue regeneration processes. In this review, we introduce a screening system that selects developmental signaling inhibitors with wide therapeutic windows using zebrafish embryonic phenotypes and provide examples of microorganism-derived Wnt pathway inhibitors. Moreover, we discuss safety prospects of the developmental signaling inhibitors.



中文翻译:

攻击后生动物胚胎发生的化学物质的驯化:鉴定改变人类发育信号通路的安全天然产物

土壤微生物是生物活性天然产物的丰富来源。种间相互作用是它们生产和改进生物活动的线索。这些在自然环境中的相互作用包括微生物和后生动物(动物)之间的相互作用,例如线虫、昆虫和蜱虫。化学细胞间通讯调节剂可以发挥理想的后生动物选择性毒性来保护微生物。发育信号通路,如 Notch、TGF-β 和 Wnt 通路,是细胞间通讯网络,有助于复杂高阶后生动物身体结构的可重复形成。发育信号通路的天然修饰剂是癌症和肉瘤治疗的有吸引力的治疗种子。然而,这些基本的信号通路也发挥着不可或缺的生理作用,它们的扰动可能导致毒性,例如干细胞生理学和组织再生过程中的缺陷。在这篇综述中,我们介绍了一种筛选系统,该系统使用斑马鱼胚胎表型选择具有广泛治疗窗口的发育信号抑制剂,并提供微生物衍生的 Wnt 通路抑制剂的示例。此外,我们还讨论了发育信号抑制剂的安全前景。我们介绍了一种筛选系统,该系统使用斑马鱼胚胎表型选择具有广泛治疗窗口的发育信号抑制剂,并提供微生物衍生的 Wnt 通路抑制剂的示例。此外,我们还讨论了发育信号抑制剂的安全前景。我们介绍了一种筛选系统,该系统使用斑马鱼胚胎表型选择具有广泛治疗窗口的发育信号抑制剂,并提供微生物衍生的 Wnt 通路抑制剂的示例。此外,我们还讨论了发育信号抑制剂的安全前景。

更新日期:2021-08-11
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