BRI2 (ITM2b) Inhibits A Deposition In Vivo
| Autor: | Maralyssa Bann, Brenda D. Moore, Neill R. Graff-Radford, Jungsu Kim, Fanggeng Zou, Lisa A. Smithson, Vijayaraghavan Rangachari, Dennis W. Dickson, Victor M. Miller, Terrone L. Rosenberry, Fredrick J. Troendle, Robert W. Price, Leilani K. Sonoda, Karen Jansen West, Christophe Verbeeck, Craig W. Zwizinski, Kayleigh Wagg, Yona Levites, Steven G. Younkin, Todd E. Golde |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Amyloid Somatic cell Transgene Mice Transgenic Biology medicine.disease_cause Article Amyloid beta-Protein Precursor Mice In vivo Cricetinae mental disorders medicine Animals Humans Adeno-associated virus Adaptor Proteins Signal Transducing Amyloid beta-Peptides Membrane Glycoproteins General Neuroscience Neurodegeneration Gene Transfer Techniques P3 peptide Brain Membrane Proteins Dependovirus medicine.disease Molecular biology Phenotype Peptide Fragments In vitro Cell biology Female Chickens |
| Zdroj: | Journal of Neuroscience. 28:6030-6036 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0891-08.2008 |
| Popis: | Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid β precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer’s disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Aβ1-40 transgenes in amyloid β protein precursor (APP) mouse models. Expression of BRI2-Aβ1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild type human BRI2 reduces cerebral Aβ deposition in an AD mouse model. Additional data indicate that the 23 amino acid peptide, Bri23, released from BRI2 by normal processing is present in human cerebrospinal fluid (CSF), inhibits Aβ aggregation in vitro, and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Aβ deposition in vivo. |
| Databáze: | OpenAIRE |
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