کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
329480 1433633 2009 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Long-term proteasome dysfunction in the mouse brain by expression of aberrant ubiquitin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Long-term proteasome dysfunction in the mouse brain by expression of aberrant ubiquitin
چکیده انگلیسی

Many neurodegenerative diseases are characterized by deposits of ubiquitinated and aberrant proteins, suggesting a failure of the ubiquitin–proteasome system (UPS). The aberrant ubiquitin UBB+1 is one of the ubiquitinated proteins accumulating in tauopathies such as Alzheimer's disease (AD) and polyglutamine diseases such as Huntington's disease. We have generated UBB+1 transgenic mouse lines with post-natal neuronal expression of UBB+1, resulting in increased levels of ubiquitinated proteins in the cortex. Moreover, by proteomic analysis, we identified expression changes in proteins involved in energy metabolism or organization of the cytoskeleton. These changes show a striking resemblance to the proteomic profiles of both AD brain and several AD mouse models. Moreover, UBB+1 transgenic mice show a deficit in contextual memory in both water maze and fear conditioning paradigms. Although UBB+1 partially inhibits the UPS in the cortex, these mice do not have an overt neurological phenotype. These mouse models do not replicate the full spectrum of AD-related changes, yet provide a tool to understand how the UPS is involved in AD pathological changes and in memory formation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 30, Issue 6, June 2009, Pages 847–863
نویسندگان
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