Neuronal overexpression of IP3 receptor 2 is detrimental in mutant SOD1 mice.
Biochem Biophys Res Commun
; 429(3-4): 210-3, 2012 Dec 14.
Article
in En
| MEDLINE
| ID: mdl-23131553
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inositol 1,4,5-Trisphosphate Receptors
/
Amyotrophic Lateral Sclerosis
/
Neurons
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2012
Type:
Article
Affiliation country:
Belgium