کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6282839 1615146 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased aggregation of polyleucine compared with that of polyglutamine in dentatorubral-pallidoluysian atrophy protein
ترجمه فارسی عنوان
افزایش تجمع پلی اکتین در مقایسه با پلی گلوامین در پروتئین آتروفی دنتاتوروبلرال-پالیدولیویسی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی
Polyglutamine (polyQ) diseases result from expansion of CAG trinucleotide repeats in their responsible genes. Although gene products with polyQ expansions undergo conformational changes to aggregate in neurons, the relationship between inclusions and neurotoxicity remains unclear. Dentatorubral-pallidoluysian atrophy (DRPLA) is a polyQ disease, and DRPLA protein, also known as atrophin-1 (ATN1), carries an expanded polyQ tract. To investigate how an expanded polyQ tract influences ATN1 aggregation and localization, we compared the aggregation of ATN1 with a polyQ tract to that of ATN1 with a polyleucine (polyL) tract. In COS-7 cells, polyL-ATN1 triggered more aggregation than polyQ-ATN1 of similar repeat sizes. Immunocytochemical and biochemical studies revealed that replacement of the polyQ tract with polyL alters ATN1 localization, leading to retention of polyL-ATN1 in the cytoplasm. Despite this change in localization, polyL-ATN1 and polyQ-ATN1 demonstrate comparable repeat length dependent toxicity. These results suggest that expanded polyQ repeats in ATN1 may contribute to neurodegeneration via alterations in both protein aggregation and intracellular localization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 552, 27 September 2013, Pages 156-161
نویسندگان
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