The E280A presenilin mutation reduces voltage-gated sodium channel levels in neuronal cells.

ABSTRACT:

Background

Familial Alzheimer's disease (FAD) mutations in presenilin (PS) modulate PS/γ-secretase activity and therefore contribute to AD pathogenesis. Previously, we found that PS/γ-secretase cleaves voltage-gated sodium channel β2-subunits (Navβ2), releases the intracellular domain of Navβ2 (β2-ICD), and thereby, increases intracellular sodium channel α-subunit Nav1.1 levels. Here, we tested whether FAD-linked PS1 mutations modulate Navβ2 cleavages and Nav1.1 levels.

Objective

It was the aim of this study to analyze the effects of PS1-linked FAD mutations on Navβ2 processing and Nav1.1 levels in neuronal cells.

Methods

We first generated B104 rat neuroblastoma cells stably expressing Navβ2 and wild-type PS1 (wtPS1), PS1 with one of three FAD mutations (E280A, M146L

SUBMITTER: Kim DY 

PROVIDER: S-EPMC3940070 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature