Mice expressing human mutant presenilin-1 exhibit decreased activation of NF-kappaB p50 in hippocampal neurons after injury.
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-kappaB 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.
Kassed
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CA
Department of Pharmacology and Therapeutics, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC 9, Tampa, FL 33612, USA.
Butler
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TL
Navidomskis
M T
MT
Gordon
M N
MN
Morgan
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Pennypacker
K R
KR
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D006624:Hippocampus / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1
D008565:Membrane Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C508853:PSEN1 protein, human; D053764:Presenilin-1