Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease
| العنوان: | Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease |
|---|---|
| المؤلفون: | Jiaqi Yao, Noel Y. Calingasan, Nina H. Pipalia, M. Flint Beal, Daniel J. Ho, Michael T. Lin |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | The Rockefeller University Press, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Genetically modified mouse, Mice, 129 Strain, Membrane lipids, Immunology, Beta-Cyclodextrins, Mice, Transgenic, Plaque, Amyloid, tau Proteins, Pharmacology, Biology, Neuroprotection, Article, Cell Line, Cell membrane, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Alzheimer Disease, Memory, medicine, Immunology and Allergy, Animals, Humans, Learning, 030304 developmental biology, 0303 health sciences, Amyloid beta-Peptides, Cholesterol, beta-Cyclodextrins, Brain, medicine.disease, Peptide Fragments, 3. Good health, 2-Hydroxypropyl-beta-cyclodextrin, Disease Models, Animal, medicine.anatomical_structure, Neuroprotective Agents, chemistry, Biochemistry, Cell culture, Alzheimer's disease, Lysosomes, 030217 neurology & neurosurgery |
| الوصف: | To be added There is extensive evidence that cholesterol and membrane lipids play a key role in Alzheimer disease (AD) pathogenesis. Cyclodextrins (CD) are cyclic oligosaccharide compounds widely used to bind cholesterol. Because CD exerts significant beneficial effects in Niemann-Pick type C disease, which shares neuropathological features with AD, we examined the effects of hydroxypropyl-β-CD (HP-β-CD) in cell and mouse models of AD. Cell membrane cholesterol accumulation was detected in N2a cells overexpressing Swedish mutant APP (SwN2a), and the level of membrane cholesterol was reduced by HP-β-CD treatment. HP-β-CD dramatically lowered the levels of Aβ42 in SwN2a cells, and the effects were persistent for 24 h after withdrawal. 4 mo of subcutaneous HP-β-CD administration significantly improved spatial learning and memory deficits in Tg19959 mice, diminished Aβ plaque deposition, and reduced tau immunoreactive dystrophic neurites. HP-β-CD lowered levels of Aβ42 in part by reducing β cleavage of the APP protein, and it also up-regulated the expression of genes involved in cholesterol transport and Aβ clearance. This is the first study to show neuroprotective effects of HP-β-CD in a transgenic mouse model of AD, both by reducing Aβ production and enhancing clearance mechanisms, which suggests a novel therapeutic strategy for AD. |
| اللغة: | English |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0387de16c3bf693451ae722356366bd http://europepmc.org/articles/PMC3526350 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c0387de16c3bf693451ae722356366bd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
|---|