Quantitative reverse-transcription polymerase chain reaction analysis of Alzheimer's-associated genes in mouse scrapie.
Prion and Alzheimer's diseases are two apparently distinct disorders; however, the two proteinaceous species implicated in disease progression share a number of common features. In prion diseases a beta-rich conformer of the prion protein is the key molecule in the pathogenesis of prion disease, whereas in Alzheimer's disease neurotoxicity is associated with the amyloid-beta peptide. These two molecules share common structural features and post-translational processing events and both undergo structural transition from normal host proteins to a form associated with toxicity, which leads to neurodegeneration. The precise mechanisms leading to neuronal damage and death that are triggered in these diseases are as yet unknown. It is possible, however, that there is a convergence of events in the neurons whereby similar pathways are executed. In this study the expression of a panel of 94 genes associated with the development of Alzheimer's disease was examined using a high-throughput real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay. Data showed that approximately 31 of these genes are deregulated in the brains of scrapie-infected mice. Among these were genes involved in inflammation, post-translational processing, excitotoxicity, cholesterol metabolism, and neuroprotection. One of the genes showing the greatest degree of upregulation was the cell cycle regulator CDC2. A microarray analysis also revealed deregulation of CDC2 and related genes, including cyclin B and cyclin D, suggesting that in prion disease, as in Alzheimer's disease, misregulation of cell cycle regulators may contribute to neurodegeneration.
Medina
Sarah
S
Molecular PathoBiology, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
Hatherall
Avril
A
Parchaliuk
Debra
D
Robertson
Catherine
C
Booth
Stephanie A
SA
D000818:Animals; D001921:Brain / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012608:Scrapie / Q000235:genetics*