Department of Medicine, Hebrew University-Hadassah Medical Centre, Jerusalem, Israel.
Pharmacol Res Perspect. 2020 Aug;8(4):e00616. doi: 10.1002/prp2.616.
Microtubules (MTs) are highly dynamic polymers that constitute the cellular cytoskeleton and play a role in multiple cellular functions. Variability characterizes biological systems and is considered a part of the normal function of cells and organs. Variability contributes to cell plasticity and is a mechanism for overcoming errors in cellular level assembly and function, and potentially the whole organ level. Dynamic instability is a feature of biological variability that characterizes the function of MTs. The dynamic behavior of MTs constitutes the basis for multiple biological processes that contribute to cellular plasticity and the timing of cell signaling. Colchicine is a MT-modifying drug that exerts anti-inflammatory and anti-cancer effects. This review discusses some of the functions of colchicine and presents a platform for introducing variability while targeting MTs in intestinal cells, the microbiome, the gut, and the systemic immune system. This platform can be used for implementing novel therapies, improving response to chronic MT-based therapies, overcoming drug resistance, exerting gut-based systemic immune responses, and generating patient-tailored dynamic therapeutic regimens.
微管(MTs)是高度动态的聚合物,构成细胞的细胞骨架,并在多种细胞功能中发挥作用。变异性是生物系统的特征,被认为是细胞和器官正常功能的一部分。变异性有助于细胞的可塑性,是克服细胞水平组装和功能错误的机制,也是整个器官水平的机制。动态不稳定性是生物变异性的一个特征,它描述了 MT 的功能。MT 的动态行为构成了多种生物学过程的基础,这些过程有助于细胞的可塑性和细胞信号转导的时间。秋水仙碱是一种 MT 修饰药物,具有抗炎和抗癌作用。本综述讨论了秋水仙碱的一些功能,并为在肠道细胞、微生物组、肠道和系统免疫系统中靶向 MT 时引入变异性提供了一个平台。该平台可用于实施新的治疗方法,提高对基于 MT 的慢性治疗的反应,克服耐药性,发挥基于肠道的系统免疫反应,并生成针对患者的动态治疗方案。