Calsenilin contributes to neuronal cell death in ischemic stroke
Journal
Brain Pathology
Journal Volume
23
Journal Issue
4
Pages
402-412
Date Issued
2013
Author(s)
Park J.-S.
Manzanero S.
Chang J.-W.
Choi Y.
Baik S.-H.
Cheng Y.-L.
Li Y.-I.
Gwon A.-R.
Woo H.-N.
Jang J.
Choi I.-Y.
Lee J.-Y.
Jung Y.-K.
Sobey C.G.
Arumugam T.V.
Jo D.-G.
Abstract
Calsenilin is a calcium sensor protein that interacts with presenilin and increases calcium-triggered neuronal apoptosis, and γ-secretase activity. Notch is a cell surface receptor that regulates cell-fate decisions and synaptic plasticity in brain. The aim of the present study was to characterize the role of calsenilin as a regulator of the γ-secretase cleavage of Notch in ischemic stroke. Here, we determined the modulation of expression level and cellular distribution of calsenilin in neurons subjected to ischemic-like conditions. The levels of calsenilin and presenilin were increased in primary neurons after oxygen and glucose deprivation. Furthermore, calsenilin was found to enhance the γ-secretase cleavage of Notch and to contribute to cell death under ischemia-like conditions. The inhibition of γ-secretase activity and a presenilin deficiency were both found to protect against calsenilin-mediated ischemic neuronal death. The expression of calsenilin was found to be increased in brain following experimental ischemic stroke. These findings establish a specific molecular mechanism by which the induction of calsenilin enhances Notch activation in ischemic stroke, and identify calsenilin as an upstream of the γ-secretase cleavage of Notch. © 2012 International Society of Neuropathology.
SDGs
Type
journal article