Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Eur J Med Chem. 2023 Jul 5;255:115404. doi: 10.1016/j.ejmech.2023.115404. Epub 2023 Apr 20.
Dual leucine zipper kinase (DLK, MAP3K12), a serine/threonine protein kinase, plays a key role in neuronal development, as it regulates axon regeneration and degeneration through its downstream kinase. Importantly, DLK is closely related to the pathogenesis of numerous neurodegenerative diseases and the induction of β-cell apoptosis that leads to diabetes. In this review, we summarize the current understanding of DLK function, and then discuss the role of DLK signaling in human diseases. Furthermore, various types of small molecule inhibitors of DLK that have been published so far are described in detail in this paper, providing some strategies for the design of DLK small molecule inhibitors in the future.
双亮氨酸拉链激酶（DLK，MAP3K12）是一种丝氨酸/苏氨酸蛋白激酶，在神经元发育中发挥关键作用，因为它通过其下游激酶调节轴突的再生和退化。重要的是，DLK与许多神经退行性疾病的发病机制以及导致糖尿病的β细胞凋亡的诱导密切相关。在这篇综述中，我们总结了目前对 DLK 功能的理解，然后讨论了 DLK 信号在人类疾病中的作用。此外，本文还详细描述了迄今为止已发表的各种类型的 DLK 小分子抑制剂，为未来 DLK 小分子抑制剂的设计提供了一些策略。
