Year: 2023
Type: review
Abstract: The past two decades have witnessed a wide range of studies investigating genetic variants of voltage‐gated sodium (Na V ) channels, which are involved in a broad spectrum of diseases, including several types of epilepsy. We have reviewed here phenotypes and pathological mechanisms of genetic epilepsies caused by variants in Na V α and β subunits, as well as of some relevant interacting proteins ( FGF12/FHF1 , PRRT2, and Ankyrin‐G). Notably, variants of all these genes can induce either gain‐ or loss‐of‐function of Na V leading to either neuronal hyperexcitability or hypoexcitability. We present the results of functional studies obtained with different experimental models, highlighting that they should be interpreted considering the features of the experimental system used. These systems are models, but they have allowed us to better understand pathophysiological issues, ameliorate diagnostics, orientate genetic counseling, and select/develop therapies within a precision medicine framework. These studies have also allowed us to gain insights into the physiological roles of different Na V channels and of the cells that express them. Overall, our review shows the progress that has been made, but also the need for further studies on aspects that have not yet been clarified. Finally, we conclude by highlighting some significant themes of general interest that can be gleaned from the results of the work of the last two decades. image
Source: Journal of Neurochemistry
DOI: 10.1111/jnc.15947
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,840
Awards: G1368826558, Idex UCA JEDI, COntinental To coastal Ecosystems: evolution, adaptability and governance, Canaux ioniques d'intérêt thérapeutique, Relation between serotoninergic brainstem dysfunction and epilepsy-related respiratory dysfunction in Dravet syndrome, Rescue of Nav1.2 Sodium Channel Functions in Severe Neurodevelopmental Disorders, Therapeutic strategies for Dravet syndrome: upregulation of endogenous SCN1A and modulation of remodeling., G8341700610, G8800819381, G880779785
OpenAlex ID: W4386347699