Voltage-Dependent Na+ Channels as Targets of BACE1 - Implications for Neuronal Firing and Beyond

Author(s): Tobias Huth, Christian Alzheimer

Journal Name: Current Alzheimer Research

Volume 9 , Issue 2 , 2012

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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

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Article Details

VOLUME: 9
ISSUE: 2
Year: 2012
Page: [184 - 188]
Pages: 5
DOI: 10.2174/156720512799361619
Price: $65

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