Background

Drugs that modulate previously unexplored targets could potentially slow or halt the progression of neurodegenerative diseases. Several candidate proteins lie within the dark kinome, those human kinases that have not been well characterized. Much of the kinome (~80%) remains poorly studied, and these targets likely harbor untapped biological potential.

Scope of review

This review highlights the significance of kinases as mediators of aberrant pathways in neurodegeneration and provides examples of published high-quality small molecules that modulate some of these kinases.

Major conclusions

There is a need for continued efforts to develop high-quality chemical tools to illuminate the function of understudied kinases in the brain. Potent and selective small molecules enable accurate pairing of an observed phenotype with a protein target.

General significance

The examples discussed herein support the premise that validation of therapeutic hypotheses surrounding kinase targets can be accomplished via small molecules and they can serve as the basis for disease-focused drug development campaigns.

中文翻译：

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描述暗激酶组在神经退行性疾病中的作用——一个小综述

背景

调节以前未探索的靶点的药物可能会减缓或阻止神经退行性疾病的进展。几种候选蛋白位于暗激酶组中，这些人类激酶尚未得到很好的表征。大部分激酶组（约 80%）的研究仍然很少，这些靶标可能蕴藏着未开发的生物学潜力。

审查范围

这篇综述强调了激酶作为神经退行性变性异常通路调节剂的重要性，并提供了已发表的调节其中一些激酶的高质量小分子的例子。

主要结论

需要继续努力开发高质量的化学工具来阐明大脑中未被充分研究的激酶的功能。有效且选择性的小分子能够将观察到的表型与蛋白质靶标准确配对。

一般意义

本文讨论的例子支持这样一个前提：围绕激酶靶标的治疗假设的验证可以通过小分子来完成，并且它们可以作为以疾病为中心的药物开发活动的基础。