دورية أكاديمية
Loss of caveolin-1 accelerates neurodegeneration and aging.
| العنوان: | Loss of caveolin-1 accelerates neurodegeneration and aging. |
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| المؤلفون: | Brian P Head, Jason N Peart, Mathivadhani Panneerselvam, Takaakira Yokoyama, Matthew L Pearn, Ingrid R Niesman, Jacqueline A Bonds, Jan M Schilling, Atsushi Miyanohara, John Headrick, Sameh S Ali, David M Roth, Piyush M Patel, Hemal H Patel |
| المصدر: | PLoS ONE, Vol 5, Iss 12, p e15697 (2010) |
| بيانات النشر: | Public Library of Science (PLoS), 2010. |
| سنة النشر: | 2010 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3009734?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0015697 |
| URL الوصول: | https://doaj.org/article/e9ff5077de67451e9e57a9790d69abee |
| رقم الأكسشن: | edsdoj.9ff5077de67451e9e57a9790d69abee |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0015697 |