Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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

Author(s): Tobias Huth and Christian Alzheimer

Volume 9, Issue 2, 2012

Page: [184 - 188] Pages: 5

DOI: 10.2174/156720512799361619

Price: $65

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


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy