Calsenilin contributes to neuronal cell death in ischemic stroke Academic Article uri icon

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.

authors

  • Park, JS
  • Manzanero, S
  • Chang, JW
  • Choi, Y
  • Baik, SH
  • Cheng, YL
  • Li, YI
  • Gwon, AR
  • Woo, HN
  • Jang, J
  • Choi, IY
  • Lee, JY
  • Jung, YK
  • Tang, SC
  • Sobey, CG
  • Arumugam, TV
  • Jo, DG

publication date

  • 2013

has subject area