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      2. west china medical publishers
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        find Keyword "Gain of function" 1 results
        • Pathogenic mechanisms and precision therapy research progress of voltage-gated sodium channels in hereditary epilepsy

          Epilepsy is a highly prevalent neurological disorder worldwide. With the widespread application of genetic testing, the critical role of genetic factors in epilepsy has been increasingly recognized. Mutations in voltage-gated sodium channels constitute the primary etiology of hereditary epilepsy. Composed of α and β subunits, these channels exhibit prominent cell-type specificity and developmental temporal dependence in their distribution across the central nervous system. Sodium channel mutations exert bidirectional pathogenic effects, namely loss of function (LOF) and gain of function (GOF). LOF mutations induce network disinhibition by impairing the function of GABAergic inhibitory interneurons, whereas GOF mutations directly amplify the firing of excitatory pyramidal neurons and trigger hyperexcitability. The combined effects of LOF and GOF determine epileptic phenotypes and drug responsiveness. This paper systematically reviews the structure, genetic characteristics and bidirectional pathogenic mechanisms of sodium channels, the phenotypic spectrum of key subtypes (SCN1A, SCN2A, SCN3A, SCN8A, SCN1B), research models, as well as precision therapeutic strategies. It provides up-to-date research advances for mechanistic investigation and individualized precision clinical diagnosis and treatment of hereditary epilepsy.

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          2. 射丝袜