期刊
MOLECULAR THERAPY
卷 18, 期 1, 页码 44-53出版社
CELL PRESS
DOI: 10.1038/mt.2009.175
关键词
-
资金
- French Agence Nationale de la Recherche [ANR07-neuro-009-03]
- Fondation de l'Avenir [ET7-480]
- Fondation NRJ-Institut de France
- Fund for Scientific Research-Flanders [G. 0038.05]
- Interuniversity Poles of Attraction [P6/43]
- Stichting voor Alzheimer Onderzoek-Fondation pour la Recherche sur la Maladie Alzheimer (SAO/FRMA)
- Institute BornBunge and University of Antwerp
- Medical Research Foundation Antwerp
- Thomas Riellaerts research fund
The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition of amyloid-beta (A beta) peptides that result in the formation of amyloid plaques, a hallmark of the pathology. In the brain, cholesterol is synthesized in situ but cannot be degraded nor cross the blood-brain barrier. The major exportable form of brain cholesterol is 24S-hydroxycholesterol, an oxysterol generated by the neuronal cholesterol 24-hydroxylase encoded by the CYP46A1 gene. We report that the injection of adeno-associated vector (AAV) encoding CYP46A1 in the cortex and hippocampus of APP23 mice before the onset of amyloid deposits markedly reduces A beta peptides, amyloid deposits and trimeric oligomers at 12 months of age. The Morris water maze (MWM) procedure also demonstrated improvement of spatial memory at 6 months, before the onset of amyloid deposits. AAV5-wtCYP46A1 vector injection in the cortex and hippocampus of amyloid precursor protein/presenilin 1 (APP/PS) mice after the onset of amyloid deposits also reduced markedly the number of amyloid plaques in the hippo-campus, and to a less extent in the cortex, 3 months after the injection. Our data demonstrate that neuronal overexpression of CYP46A1 before or after the onset of amyloid plaques significantly reduces A beta pathology in mouse models of AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据