AUTHOR=Zou Shuang , Lan Yu-Long , Gong Yiwei , Chen Zhong , Xu Cenglin 

TITLE=The role of ATP1A3 gene in epilepsy: We need to know more

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1143956

DOI=10.3389/fncel.2023.1143956

ISSN=1662-5102

ABSTRACT=<p>The <italic>ATP1A3</italic> gene, which encodes the Na<sup>+</sup>/K<sup>+</sup>-ATPase α3 catalytic subunit, plays a crucial role in both physiological and pathological conditions in the brain, and mutations in this gene have been associated with a wide variety of neurological diseases by impacting the whole infant development stages. Cumulative clinical evidence suggests that some severe epileptic syndromes have been linked to mutations in <italic>ATP1A3</italic>, among which inactivating mutation of <italic>ATP1A3</italic> has been intriguingly found to be a candidate pathogenesis for complex partial and generalized seizures, proposing <italic>ATP1A3</italic> regulators as putative targets for the rational design of antiepileptic therapies. In this review, we introduced the physiological function of <italic>ATP1A3</italic> and summarized the findings about <italic>ATP1A3</italic> in epileptic conditions from both clinical and laboratory aspects at first. Then, some possible mechanisms of how <italic>ATP1A3</italic> mutations result in epilepsy are provided. We think this review timely introduces the potential contribution of <italic>ATP1A3</italic> mutations in both the genesis and progression of epilepsy. Taken that both the detailed mechanisms and therapeutic significance of <italic>ATP1A3</italic> for epilepsy are not yet fully illustrated, we think that both in-depth mechanisms investigations and systematic intervention experiments targeting <italic>ATP1A3</italic> are needed, and by doing so, perhaps a new light can be shed on treating <italic>ATP1A3</italic>-associated epilepsy.</p>