| First Author | Yu Z | Year | 2000 |
| Journal | J Mol Neurosci | Volume | 15 |
| Issue | 1 | Pages | 31-44 |
| PubMed ID | 11211235 | Mgi Jnum | J:117914 |
| Mgi Id | MGI:3697981 | Doi | 10.1385/JMN:15:1:31 |
| Citation | Yu Z, et al. (2000) Neuroprotective role for the p50 subunit of NF-kappaB in an experimental model of Huntington's disease. J Mol Neurosci 15(1):31-44 |
| abstractText | Prototypical NF-kappaB consists of a transcription factor dimer of p50 and p65, and an inhibitory subunit called I-kappaB. NF-kappaB is activated in neurons in response to excitotoxic, metabolic, and oxidative stress. Cell-culture data suggest that activation of NF-kappaB can prevent neuronal apoptosis, but its role in vivo is unclear and the specific kappaB subunits involved are unknown. In Huntington's disease (HD), striatal neurons degenerate, and a similar pattern of neuronal vulnerability occurs in rats and mice following exposure to the mitochondrial toxin 3-nitropropionic acid (3NP). We report that mice lacking the p50 subunit of NF-kappaB exhibit increased damage to striatal neurons following administration of 3NP. The neuronal death occurs by apoptosis as indicated by increased caspase activation and DNA fragmentation into oligonucleosomes. NF-kappaB activity is markedly increased in striatum 24-72 h following 3NP administration in wild-type mice, but not in mice lacking p50, indicating that p50 is necessary for the vast majority of 3NP-induced NF-kappaB DNA-binding activity in striatum. Cultured striatal neurons from p50-/- mice exhibited enhanced oxidative stress, perturbed calcium regulation, and increased cell death following exposure to 3NP, suggesting a direct adverse effect of p50 deficiency in striatal neurons. |
