Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders.
Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders.
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DOI：
10.3389/fnmol.2021.655037
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发表时间：
2021
影响因子：
4.8
通讯作者：
Xiao L
中科院分区：
文献类型：
--
作者：
Hu C;Feng P;Yang Q;Xiao L
尽管神经发育障碍（NDD）从基因型到表型都很复杂，但在过去的几十年里，人们在理解其病理生理学方面取得了实质性进展。最近积累的证据表明，千零一个 (TAO) 激酶的遗传变异与多种 NDD 的主要贡献者相关。尽管众所周知，TAO 激酶是一个高度保守的 STE20 激酶家族，在多种生物过程中发挥着重要作用，但 TAO 激酶在神经发育和 NDD 中的新兴作用尚未得到深入讨论。在这篇综述文章中，我们基于结构和生化分析总结了 TAO 激酶的潜在作用，提供了临床研究的遗传数据，并评估了 TAO 激酶突变、神经病理学和 NDD 行为障碍之间的机制联系。然后，我们提供从基础研究到临床治疗的潜在观点，这可能有助于充分理解 TAO 激酶如何参与 NDD。
Despite the complexity of neurodevelopmental disorders (NDDs), from their genotype to phenotype, in the last few decades substantial progress has been made in understanding their pathophysiology. Recent accumulating evidence shows the relevance of genetic variants in thousand and one (TAO) kinases as major contributors to several NDDs. Although it is well-known that TAO kinases are a highly conserved family of STE20 kinase and play important roles in multiple biological processes, the emerging roles of TAO kinases in neurodevelopment and NDDs have yet to be intensively discussed. In this review article, we summarize the potential roles of the TAO kinases based on structural and biochemical analyses, present the genetic data from clinical investigations, and assess the mechanistic link between the mutations of TAO kinases, neuropathology, and behavioral impairment in NDDs. We then offer potential perspectives from basic research to clinical therapies, which may contribute to fully understanding how TAO kinases are involved in NDDs.
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