| First Author | Staats KA | Year | 2013 |
| Journal | Neurobiol Dis | Volume | 60 |
| Pages | 11-7 | PubMed ID | 23969236 |
| Mgi Jnum | J:201756 | Mgi Id | MGI:5515668 |
| Doi | 10.1016/j.nbd.2013.08.006 | Citation | Staats KA, et al. (2013) Genetic ablation of phospholipase C delta 1 increases survival in SOD1(G93A) mice. Neurobiol Dis 60:11-7 |
| abstractText | Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease, resulting in selective motor neuron degeneration and paralysis. Patients die approximately 3-5years after diagnosis. Disease pathophysiology is multifactorial, including excitotoxicity, but is not yet fully understood. Genetic analysis has proven fruitful in the past to further understand genes modulating the disease and increase knowledge of disease mechanisms. Here, we revisit a previously performed microsatellite analysis in ALS and focus on another hit, PLCD1, encoding phospholipase C delta 1 (PLCdelta1), to investigate its role in ALS. PLCdelta1 may contribute to excitotoxicity as it increases inositol 1,4,5-trisphosphate (IP3) formation, which releases calcium from the endoplasmic reticulum through IP3 receptors. We find that expression of PLCdelta1 is increased in ALS mouse spinal cord and in neurons from ALS mice. Furthermore, genetic ablation of this protein in ALS mice significantly increases survival, but does not affect astrogliosis, microgliosis, aggregation or the amount of motor neurons at end stage compared to ALS mice with PLCdelta1. Interestingly, genetic ablation of PLCdelta1 prevents nuclear shrinkage of motor neurons in ALS mice at end stage. These results indicate that PLCD1 contributes to ALS and that PLCdelta1 may be a new target for future studies. |
