Deciphering the multifunctional role of dual leucine zipper kinase (DLK) and its therapeutic potential in disease

被引：3

作者：

Bu, Haiqing ^{[1
]}

Li, Zhijia ^{[1
]}

Lu, Yingying ^{[1
]}

Zhuang, Zhiyao ^{[1
]}

Zhen, Yongqi ^{[2
,3
]}

Zhang, Lan ^{[1
]}

机构：

[1] Southwest Jiaotong Univ, Sch Life Sci & Engn, Sichuan Engn Res Ctr Biomimet Synth Nat Drugs, Chengdu 610031, Peoples R China

[2] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[3] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 255卷

基金：

中国国家自然科学基金;

关键词：

DLK; Structure; Regeneration and degeneration of axons; Neurodegenerative diseases; Diabetes; Small molecule inhibitors; ACTIVATED PROTEIN-KINASE; INSULIN GENE-TRANSCRIPTION; N-TERMINAL KINASE; INDUCED PERIPHERAL NEUROPATHY; AXON SELF-DESTRUCTION; DRUGS CYCLOSPORINE-A; BEARING KINASE; TISSUE TRANSGLUTAMINASE; BETA-CELLS; MEMBRANE DEPOLARIZATION;

D O I：

10.1016/j.ejmech.2023.115404

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 beta-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.

引用

页数：17

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