Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration Miniperspective

被引：40

作者：

Siu, Michael ^{[1
]}

Ghosh, Arundhati Sengupta ^{[1
]}

Lewcock, Joseph W. ^{[2
]}

机构：

[1] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA

[2] Denali Therapeut, 151 Oyster Point Blvd, San Francisco, CA 94080 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 18期

关键词：

MIXED-LINEAGE KINASE-3; GANGLION-CELL DEATH; AXONAL INJURY; BEARING KINASE; NEURONAL DEGENERATION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; SIGNALING PATHWAY; IN-VIVO; DLK;

D O I：

10.1021/acs.jmedchem.8b00370

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and describe selected small molecules that have been utilized to inhibit DLK kinase activity in vivo. These compounds represent valuable tools for understanding the role of DLK signaling and evaluating the potential for DLK inhibition as a therapeutic strategy to prevent neuronal degeneration.

引用

页码：8078 / 8087

页数：10

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