Mutations in the presenilin-1 (mutPS-1) gene, a cause of familial Alzheimer's disease, increase the susceptibility of neurons to apoptotic death. Using the trimethyltin model of hippocampal neurodegeneration, mice expressing the human mutPS-1 gene (M146L) exhibited increased neurodegeneration and mortality relative to non-transgenic littermates. Activation of NF-κB p50 was found to be impaired in transgenic mice with unaltered expression levels suggesting that mutPS-1 expression inhibits p50 activation to adversely affect neuronal resistance to injury.
|Number of pages||6|
|Journal||Molecular Brain Research|
|State||Published - Jan 31 2003|
Bibliographical noteFunding Information:
This research was supported by NIH Grant RO1 NS39141-01A2 and American Heart Association Grants 9930072N (K.R.P.) and 0120233B (T.L.B.).
- Presenilin-1 gene mutations
- Resistance to injury
- Signal transduction
- Transcription factors
- mutPS-1 mice
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience