کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4932799 | 1433529 | 2017 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease N-type Ca2+ channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease](/preview/png/4932799.png)
چکیده انگلیسی
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca2+ channels (Cav2.2), which are essential for presynaptic neurotransmitter release. Thus, to elucidate the mechanism underlying mutant htt-mediated alterations in neurotransmission, we investigated how Cav2.2 is affected by full-length mutant htt expression in a mouse model of HD (BACHD). Our data indicate that young BACHD mice exhibit increased striatal glutamate release, which is reduced to wild type levels following Cav2.2 block. Cav2.2 Ca2+ current-density and plasma membrane expression are increased in BACHD mice, which could account for increased glutamate release. Moreover, mutant htt affects the interaction between Cav2.2 and 2 major channel regulators, namely syntaxin 1A and Gβγ protein. Notably, 12-month old BACHD mice exhibit decreased Cav2.2 cell surface expression and glutamate release, suggesting that Cav2.2 alterations vary according to disease stage.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 55, July 2017, Pages 1-10
Journal: Neurobiology of Aging - Volume 55, July 2017, Pages 1-10
نویسندگان
Flavia R. Silva, Artur S. Miranda, Rebeca P.M. Santos, Isabella G. Olmo, Gerald W. Zamponi, Tomas Dobransky, Jader S. Cruz, Luciene B. Vieira, Fabiola M. Ribeiro,