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Neurosci Lett. 2010 Dec 10;486(2):68-72. doi: 10.1016/j.neulet.2010.08.048. Epub 2010 Sep 15.

Alzheimer's secretases regulate voltage-gated sodium channels.

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  • 1Neurobiology of Disease Laboratory, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.


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

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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