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  • Title: Alzheimer's secretases regulate voltage-gated sodium channels.
    Author: Kovacs DM, Gersbacher MT, Kim DY.
    Journal: Neurosci Lett; 2010 Dec 10; 486(2):68-72. PubMed ID: 20817076.
    Abstract:
    BACE1 and presenilin (PS)/γ-secretase are primary proteolytic enzymes responsible for the generation of pathogenic amyloid β-peptides (Aβ) in Alzheimer's disease. We and others have found that β-subunits of the voltage-gated sodium channel (Na(v)βs) also undergo sequential proteolytic cleavages mediated by BACE1 and PS/γ-secretase. In a follow-up study, we reported that elevated BACE1 activity regulates total and surface expression of voltage-gated sodium channels (Na(v)1 channels) and thereby modulates sodium currents in neuronal cells and mouse brains. In this review, we focus on the molecular mechanism of how BACE1 and PS/γ-secretase regulate Na(v)1 channels in neuronal cells. We will also discuss potential physiological and pathological roles of BACE1- and PS/γ-secretase-mediated processing of Na(v)βs in relation to Na(v)1 channel function.
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