کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6806960 1433578 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tenascin-C deficiency ameliorates Alzheimer's disease-related pathology in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Tenascin-C deficiency ameliorates Alzheimer's disease-related pathology in mice
چکیده انگلیسی
Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposits of amyloid β peptide (Aβ) and microglia-driven inflammatory activation. Tenascin-C (tnc) is an extracellular matrix protein that is upregulated in inflammation and induces further inflammatory responses. We hypothesized that tnc contributes to the inflammatory pathology in AD. Using real-time polymerase chain reaction, we observed that tnc gene transcription was upregulated in cultured microglia after Aβ challenge and in the brain of an AD mouse model that overexpresses mutated amyloid precursor protein (APP) in neural cells. By cross-breeding APP-transgenic mice and tenascin-C-deficient mice, we demonstrated using real-time polymerase chain reaction, Western blot analysis, enzyme-linked immunosorbent assay, and immunohistochemistry that tnc deficiency reduces pro- but enhances anti-inflammatory activation in the mutated APP-transgenic mouse brain, associated with a reduced cerebral Aβ load and higher levels of the postsynaptic density protein 95. Thus, our study indicates that functional inhibition of tnc exerts beneficial effects on AD pathogenesis, suggesting a potential for tnc as a new therapeutic target in AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 34, Issue 10, October 2013, Pages 2389-2398
نویسندگان
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