Hu Chun, Feng Pan, Yang Qian, Xiao Lin
Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, South China Normal University, Guangzhou, China.
Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China.
Front Mol Neurosci. 2021 Mar 24;14:655037. doi: 10.3389/fnmol.2021.655037. eCollection 2021.
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.
尽管神经发育障碍（NDDs）从基因型到表型都很复杂，但在过去几十年里，人们在理解其病理生理学方面取得了重大进展。最近越来越多的证据表明，千与一（TAO）激酶中的基因变异是多种NDDs的主要促成因素。虽然众所周知TAO激酶是STE20激酶的一个高度保守的家族，并且在多个生物学过程中发挥重要作用，但TAO激酶在神经发育和NDDs中的新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，展示了临床研究中的基因数据，并评估了TAO激酶突变、神经病理学和NDDs行为障碍之间的机制联系。然后，我们从基础研究到临床治疗提供了潜在的观点，这可能有助于全面理解TAO激酶如何参与NDDs。
