Calsenilin contributes to neuronal cell death in ischemic stroke

Jong Sung Park, Silvia Manzanero, Jae Woong Chang, Yuri Choi, Sang Ha Baik, Yi Lin Cheng, Yu I. Li, A. Ryeong Gwon, Ha Na Woo, Jiyeon Jang, In Young Choi, Joo Yong Lee, Yong Keun Jung, Sung Chun Tang, Christopher G. Sobey, Thiruma V. Arumugam, Dong Gyu Jo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)402-412
Number of pages11
JournalBrain Pathology
Issue number4
StatePublished - Jul 2013


  • Notch
  • calsenilin
  • ischemic stroke
  • neuronal cell death
  • γ-secretase


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