کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6274067 1614814 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inactivation of Apaf1 reduces the formation of mutant huntingtin-dependent aggregates and cell death
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Inactivation of Apaf1 reduces the formation of mutant huntingtin-dependent aggregates and cell death
چکیده انگلیسی
Polyglutamine expansions in some proteins associated with neurodegenerative diseases, such as Huntington's disease or several ataxias, lead to insoluble aggregates in the cell. These aggregates accumulate through a mechanism that is not yet fully understood, but it activates cell death pathways and contributes to kill the cell. Here, we show that apoptotic protease activating factor 1 (Apaf1) down-regulation, or treatment with pharmacological Apaf1 inhibitor SVT016426, decreases both polyglutamine-induced aggregation and polyglutamine-induced apoptotic cell death in different cellular models. We demonstrate that Apaf1 binds to both Htt and to heat shock protein chaperone Hsp70, and that this interaction is altered in the presence of the pharmacological inhibitor of Apaf1. Based on our findings, we hypothesize that Apaf1 enhances polyglutamine aggregation by reducing the cellular protein levels of available functional Hsp70.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 262, 14 March 2014, Pages 83-91
نویسندگان
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