کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4322444 1291708 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
چکیده انگلیسی

SummaryNeurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). We generated two antibodies specific for acetylated tau and showed that tau acetylation is elevated in patients at early and moderate Braak stages of tauopathy. Histone acetyltransferase p300 was involved in tau acetylation and the class III protein deacetylase SIRT1 in deacetylation. Deleting SIRT1 enhanced levels of acetylated-tau and pathogenic forms of p-tau, probably by blocking proteasome-mediated degradation. Inhibiting p300 with a small molecule promoted tau deacetylation and eliminated p-tau associated with tauopathy. Modulating tau acetylation could be a new therapeutic strategy to reduce tau-mediated neurodegeneration.


► Tau is acetylated and tau acetylation is elevated at early stage of tauopathy
► SIRT1 deacetylates tau, whereas p300 mediates tau acetylation
► Tau acetylation slows down its degradation
► Enhancing tau deacetylation abolishes pathogenic forms of phosphorylated tau

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 67, Issue 6, 23 September 2010, Pages 953–966
نویسندگان
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