Alzheimer's secretases regulate voltage-gated sodium channels

NEUROSCIENCE LETTERS

卷:486

Review

Kovacs, Dora M.¹  Gersbacher, Manuel T.¹  Kim, Doo Yeon¹ 

[1] Harvard Univ, Massachusetts Gen Hosp, Neurobiol Dis Lab,Sch Med, Genet & Aging Res Unit,MassGen Inst Neurodegenera, Charlestown, MA 02129 USA

关键词: Alzheimer's disease;    BACE1;    beta-Secretase;    Presenilin;    gamma-Secretase;    Voltage-gated sodium channel;    Sodium channel beta 2-subnit;   

DOI  :  10.1016/j.neulet.2010.08.048

来源: Elsevier

【 摘 要 】

BACE1 and presenilin (PS)/gamma-secretase are primary proteolytic enzymes responsible for the generation of pathogenic amyloid beta-peptides (A beta) in Alzheimer's disease. We and others have found that beta-subunits of the voltage-gated sodium channel (Na-v beta s) also undergo sequential proteolytic cleavages mediated by BACE1 and PS/gamma-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/gamma-secretase regulate Na(v)1 channels in neuronal cells. We will also discuss potential physiological and pathological roles of BACE1- and PS/gamma-secretase-mediated processing of Na-v beta s in relation to Na(v)1 channel function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free