Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.
Denali Therapeutics , 151 Oyster Point Boulevard , South San Francisco , California 94080 , United States.
J Med Chem. 2018 Sep 27;61(18):8078-8087. doi: 10.1021/acs.jmedchem.8b00370. Epub 2018 Jun 4.
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.
双亮氨酸拉链激酶（DLK，MAP3K12）是神经元应激反应的必需驱动因子，可调节急性神经元损伤和慢性神经退行性疾病（如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）模型中的神经退行性变。在这篇综述中，我们提供了 DLK 信号机制的概述，并描述了一些已被用于体内抑制 DLK 激酶活性的小分子。这些化合物是理解 DLK 信号作用的有价值的工具，并评估了 DLK 抑制作为预防神经元变性的治疗策略的潜力。
