کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6021525 1580638 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Striatal NELF-mediated RNA polymerase II stalling controls l-dopa induced dyskinesia
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Striatal NELF-mediated RNA polymerase II stalling controls l-dopa induced dyskinesia
چکیده انگلیسی
Long-term l-3,4-dihydroxyphenylalanine (l-Dopa) treatment in Parkinson's disease leads to involuntary movements called dyskinesia, notably through an overexpression of immediate-early genes (IEG). Their rapid transcription involves the stalling of RNA polymerase II on IEG promoters, a mechanism that critically depends on the presence of the negative elongation factor (NELF) protein complex. We here down-regulated the key NELF-E subunit using lentiviral vector delivery of a short hairpin RNA in the striatum of 6-hydroxydopamine lesioned rats. Such NELF-E reduced expression significantly attenuated the development of abnormal involuntary movements in response to chronic l-Dopa treatment. Effectiveness of silencing was demonstrated by the significant decrease in striatal ∆ FosB, ARC and Zif268 IEG expression. Repression of NELF-mediating RNA polymerase II stalling thus achieves both antidyskinetic and potentiation of antiparkinsonian l-Dopa effect, highlighting the role of transcriptional events in dyskinesia establishment, acute dyskinetic manifestation and in the therapeutic response to l-Dopa.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 85, January 2016, Pages 93-98
نویسندگان
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