College of Pharmacy, Jinan University, Guangzhou 511443, Guangdong Province, China.
World J Gastroenterol. 2024 Nov 7;30(41):4509-4513. doi: 10.3748/wjg.v30.i41.4509.
We summarize the mechanism by which taurine (Tau) inhibits autophagy and induces iron apoptosis in hepatic stellate cells. Tau interacts with autophagy regulates multifunctional proteins, microtubule-associated protein 1 light chain 3 Beta, and autophagy-related gene 5 to inhibit autophagy, binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy, and interacts with glutathione peroxidase 4 to promote iron apoptosis. There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation. From a pharmaceutical point of view, there are certain requirements for Tau protein delivery systems, such as loading efficiency, stability, and targeting. Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency. Since Tau is a hydrophilic molecule with high water solubility, liposomes, micelles, and amphiphilic polymer nanoparticles may represent a superior choice. The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs, respectively, whereas Tau is expected to be loaded into the water region. In addition, a representative method of actively targeting hematopoietic stem cells is introduced. A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes (lecithin plus cholesterol).
我们总结了牛磺酸（Tau）抑制自噬并诱导肝星状细胞中铁凋亡的机制。Tau 与自噬调节多功能蛋白相互作用，微管相关蛋白 1 轻链 3 Beta 和自噬相关基因 5 抑制自噬，与铁蛋白重链 1 和核受体共激活因子 4 结合引发铁蛋白自噬，并与谷胱甘肽过氧化物酶 4 相互作用促进铁凋亡。开发针对自噬和铁死亡调节的 Tau 基疗法具有坚实的理论依据。从药物的角度来看，Tau 蛋白递药系统有一定的要求，如载药效率、稳定性和靶向性。纳米材料还应含有类似于 Tau 的亲水基序，以优化载药效率。由于 Tau 是一种具有高水溶性的亲水分子，脂质体、胶束和两亲聚合物纳米粒可能是更好的选择。脂质体的纳米结构包括水相和脂质膜，分别隔离亲水性和疏水性药物，而 Tau 有望被载入水相。此外，还介绍了一种主动靶向造血干细胞的代表性方法。基于常见脂质体（卵磷脂加胆固醇）的配方，提出了一种基于 Tau 的肝纤维化治疗方法。
