Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's Disease
| العنوان: | Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's Disease |
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| المؤلفون: | Ornella Ahouansou, Patrick Aubourg, Abdellatif Benraiss, Femke S. Stet, Eloise Hudry, André Delacourte, Pierre Bougnères, Debby Van Dam, Wim Kulik, Nathalie Cartier, Peter Paul De Deyn |
| المساهمون: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases |
| المصدر: | Molecular therapy Molecular therapy, 18(1), 44-53. Nature Publishing Group |
| بيانات النشر: | Elsevier BV, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Amyloid, medicine.medical_specialty, Blotting, Western, BACE1-AS, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, Biology, Presenilin, Cell Line, Mice, Alzheimer Disease, Internal medicine, mental disorders, Drug Discovery, Cholesterol 24-Hydroxylase, Genetics, medicine, Amyloid precursor protein, Animals, Humans, Senile plaques, Molecular Biology, Pharmacology, Reverse Transcriptase Polymerase Chain Reaction, P3 peptide, Genetic Therapy, Original Articles, Dependovirus, medicine.disease, Immunohistochemistry, Molecular biology, Hydroxycholesterols, Biochemistry of Alzheimer's disease, Endocrinology, Steroid Hydroxylases, biology.protein, Molecular Medicine, Human medicine, Alzheimer's disease |
| الوصف: | The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition of amyloid-beta (Abeta) 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 Abeta 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 hippocampus, 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 Abeta pathology in mouse models of AD. |
| وصف الملف: | |
| تدمد: | 1525-0016 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45c1f680161ca1ab88f60206fe8f93f8Test https://doi.org/10.1038/mt.2009.175Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....45c1f680161ca1ab88f60206fe8f93f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15250016 |
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