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 Alzheimers 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.
Keywords: BACE1, voltage-dependent sodium channel, -subunit, action potential, neuronal excitability, epilepsy, hippocampus, Alzheimer's disease, C-terminal fragment
Current Alzheimer Research
Title: Voltage-Dependent Na+ Channels as Targets of BACE1 - Implications for Neuronal Firing and Beyond
Volume: 9 Issue: 2
Author(s): Tobias Huth and Christian Alzheimer
Affiliation:
Keywords: BACE1, voltage-dependent sodium channel, -subunit, action potential, neuronal excitability, epilepsy, hippocampus, Alzheimer's disease, C-terminal fragment
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 Alzheimers 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.
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Cite this article as:
Huth Tobias and Alzheimer Christian, Voltage-Dependent Na+ Channels as Targets of BACE1 - Implications for Neuronal Firing and Beyond, Current Alzheimer Research 2012; 9 (2) . https://dx.doi.org/10.2174/156720512799361619
DOI https://dx.doi.org/10.2174/156720512799361619 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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