Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

Front Mol Neurosci. 2021 Mar 24;14:655037. doi: 10.3389/fnmol.2021.655037. eCollection 2021.

Abstract

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.

Keywords: TAO kinase; cytoskeleton; de novo mutations; neurodevelopmental disorders; neuron; therapy.