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-l Li, A-Ryeong Gwon, Ha-Na Woo, Jiyeon Jang, In-Young Choi, Joo-Yong Lee, Yong-Keun Jung, Sung-Chun Tang, Christopher Graeme Sobey, Thiruma Arumugam, Dong-Gyu Jo

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9 Citations (Scopus)


Calsenilin is a calcium sensor protein that interacts with presenilin and increases calcium-triggered neuronal apoptosis, and gamma-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 gamma-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 gamma-secretase cleavage of Notch and to contribute to cell death under ischemia-like conditions. The inhibition of gamma-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 gamma-secretase cleavage of Notch.
Original languageEnglish
Pages (from-to)402 - 412
Number of pages11
JournalBrain Pathology
Issue number4
Publication statusPublished - 2013

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