کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259206 | 1534632 | 2016 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Loss of striatal 90-kDa ribosomal S6 kinase (Rsk) is a key factor for motor, synaptic and transcription dysfunction in Huntington's disease
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کلمات کلیدی
GFPRSKMSKhttIEGsPSD95VGLUT1SRFAAV5RPMBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز Striatum - استریاتومHuntington's disease - بیماری هانتینگتونBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزserum response factor - فاکتور پاسخ سرمیHuntingtin - هانتینگتنgreen fluorescent protein - پروتئین فلورسنت سبزmitogen- and stress-activated protein kinase - پروتئین کیناز متیوژن و استرس فعالrotations per minute - چرخش در دقیقه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Huntington's disease (HD) is characterized by motor dysfunction due to the expression of mutant huntingtin that promotes degeneration of striatal GABAergic medium-sized spiny neurons. Here we explore the role of the 90-kDa ribosomal S6 kinase (Rsk) in the physiopathology of HD. First, we show a reduction of Rsk1 and 2 protein levels in the striatum of two HD mouse models, R6/1 and HdhQ7/Q111 knock-in mice, at ages when they suffer from motor disturbances. Interestingly, the analysis of post-mortem samples from HD patients revealed a significant reduction of both Rsk forms in the putamen and caudate, but not in the cortex. Rsk1 and 2 levels were also reduced in the striatum of BDNF heterozygous mice, and upon BDNF neutralization in striatal cultures, suggesting that striatal loss of BDNF could be involved in the decrease of Rsk levels. Finally, we injected recombinant adeno-associated-virus (AAV5)-Rsk in the striatum of R6/1 mice at the onset of motor symptoms. Four weeks later, we found higher Rsk levels in the striatum accompanied by improvements in motor coordination, enhanced expression of synaptic markers and increased expression of genes related to synaptic plasticity, such as cfos and egr1. Altogether, we identified Rsk as a key factor in striatal alterations associated with motor deficits in HD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 7, July 2016, Pages 1255-1266
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 7, July 2016, Pages 1255-1266
نویسندگان
Marta Anglada-Huguet, Albert Giralt, Laura Rué, Jordi Alberch, Xavier Xifró,