Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

  • 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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center