Lifespan Profiles of Alzheimer's Disease-Associated Genes and Products in Monkeys and Mice
| Autor: | Lina Adwan, Nasser H. Zawia, Deborah C. Rice, Debomoy K. Lahiri, Christopher A. McPherson, G. Jean Harry, Remi Dosunmu, Riyaz Basha, Jinfang Wu, Bryan Maloney |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Longevity Biology Article Pathogenesis Mice Random Allocation Species Specificity Alzheimer Disease Transcription (biology) mental disorders Transcriptional regulation medicine Animals Humans Protein precursor Transcription factor Gene Messenger RNA General Neuroscience Age Factors Haplorhini General Medicine medicine.disease Molecular biology Mice Inbred C57BL Macaca fascicularis Psychiatry and Mental health Clinical Psychology Geriatrics and Gerontology Alzheimer's disease Transcription Factors |
| Zdroj: | Journal of Alzheimer's Disease. 18:211-230 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Alzheimer's disease (AD) is characterized by plaques of amyloid-beta (Abeta) peptide, cleaved from amyloid-beta protein precursor (AbetaPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 (SP1), and the beta amyloid precursor cleaving enzyme (BACE1). In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. |
| Databáze: | OpenAIRE |
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