title: Voltage-dependent Na+ channels as targets of BACE1 - implications for neuronal firing and beyond.
abstract: Voltage-dependent sodium channel complexes consist of a pore-forming and voltage-sensing α-subunit and one or two β-subunits. The latter are type I transmembrane proteins with a broad spectrum of functions in channel expression and surface targeting, in channel electrophysiology and, notably, in cell-adhesion of excitable and non-excitable cells. Like the amyloid-precursor protein (APP), β-subunits are substrates for sequential cleavage either by α- and γ-secretase, or by β- and γ-secretase. Here, we focus on the processing of β-subunits by the amyloidogenic β-secretase, BACE1, which is up-regulated in Alzheimer's disease and is considered a highly promising pharmacologic target. Based on data from BACE1-deficient or over-expressing mice and from heterologous expression systems, this review summarizes our growing understanding of how BACE1-mediated cleavage of β-subunits interferes with their multiple physiological functions.
authors.affiliation: Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Huth
authors.forename: Christian
authors.initials: C
authors.lastname: Alzheimer
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015222:Sodium Channels; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human