Title: Neuronal overexpression of IP(3) receptor 2 is detrimental in mutant SOD1 mice
Authors: Staats, Kim
Bogaert, Elke
Hersmus, Nicole
Jaspers, Tom
Luyten, Tomas
Bultynck, Geert
Parys, Jan
Hisatsune, Chihiro
Mikoshiba, Katsuhiko
Van Damme, Philip
Robberecht, Wim
Van Den Bosch, Ludo # ×
Issue Date: 14-Dec-2012
Publisher: Academic Press
Series Title: Biochemical and Biophysical Research Communications vol:429 issue:3-4 pages:210-213
Article number: S0006-291X(12)02086-4
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease causing progressive paralysis of the patient followed by death on average 3-5 years after diagnosis. Disease pathology is multi-factorial including the process of excitotoxicity that induces cell death by cytosolic Ca(2+) overload. In this study, we increased the neuronal expression of an endoplasmic reticulum (ER) Ca(2+) release channel, inositol 1,4,5-trisphosphate receptor 2 (IP(3)R2), to assess whether increased cytosolic Ca(2+) originating from the ER is detrimental for neurons. Overexpression of IP(3)R2 in N2a cells using a Thy1.2-IP(3)R2 construct increases cytosolic Ca(2+) concentrations evoked by bradykinin. In addition, mice generated from this construct have increased expression of IP(3)R2 in the spinal cord and brain. This overexpression of IP(3)R2 does not affect symptom onset, but decreases disease duration and shortens the lifespan of the ALS mice significantly. These data suggest that ER Ca(2+) released by IP(3) receptors may be detrimental in ALS and that motor neurons are vulnerable to impaired Ca(2+) metabolism.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular and Cellular Signaling
Laboratory for Neurobiology
× corresponding author
# (joint) last author

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