Alzheimer's secretases regulate voltage-gated sodium channels

▶ BACE1 and γ-secretase sequentially cleave the sodium channel β2-subunit. ▶ Sequential cleavage of the β2-subunit releases its intracellular domain. ▶ The intracellular domain of the β2-subunit localizes into nucleus. ▶ β2-subunit's intracellular domain regulates sodium channel α-subunit, Nav1.1 levels. ▶ Elevated BACE1 activity dramatically decreases surface Nav1.1 levels in neuronal cells.