کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9989706 | 1580764 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A human single-chain Fv intrabody preferentially targets amino-terminal huntingtin fragments in striatal models of Huntington's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Amino-terminal fragments of huntingtin (htt) appear to result from proteolytic processing of the full-length protein in Huntington's disease (HD), and fragments containing pathological expansions of polyglutamine elicit toxicity in model systems. Such fragments are sequestered into insoluble aggregates, which may initially serve a cellular protective mechanism, while soluble fragments and/or oligomers may be a more acute toxic species. Agents which enhance mutant htt clearance have shown therapeutic potential in animal models of HD. Here, we present the first evidence of an htt-specific single-chain Fv intrabody (C4) that selectively targets the soluble fraction of amino-terminal htt fragments. Our findings suggest that the C4 intrabody binds weakly, but does not alter the levels of endogenous, full-length htt. C4 appears to decrease the steady-state levels of amino-terminal htt fragments by binding to non-aggregated, but not aggregated, htt species. Intrabodies may be used as potential curative agents, and as drug discovery tools, for HD and other misfolded protein disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 19, Issues 1â2, JuneâJuly 2005, Pages 47-56
Journal: Neurobiology of Disease - Volume 19, Issues 1â2, JuneâJuly 2005, Pages 47-56
نویسندگان
Todd W. Miller, Chun Zhou, Silvia Gines, Marcy E. MacDonald, Nicholas D. Mazarakis, Gillian P. Bates, James S. Huston, Anne Messer,