کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6803259 | 1433537 | 2016 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tissue remodeling after interference RNA mediated knockdown of transthyretin in a familial amyloidotic polyneuropathy mouse model
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Transthyretin (TTR) deposition in the peripheral nervous system is the hallmark of familial amyloidotic polyneuropathy (FAP). Currently, liver transplantation is the only available treatment to halt the progression of clinical symptoms; however, due to the limitations of this procedure, development of alternative therapeutic strategies is of utmost importance. In this regard, interference RNA (RNAi) targeting TTR is currently in phase III clinical development. To dissect molecular changes occurring in dorsal root ganglia (DRG) upon RNAi-mediated knockdown of TTR, we treated both chronically and acutely an FAP mouse model, in different stages of disease. Our data show that inhibition of TTR expression by the liver with RNAi reverse TTR deposition in DRG, decrease matrix metalloproteinase-2 (MMP-2) protein levels in plasma, inhibit Mmp-2 gene expression and downregulate MMP-9 activity in DRG, indicating extracellular matrix remodeling. Furthermore, protein levels of MMP-2 were found upregulated in plasma samples from FAP patients indicating that MMP-2 might be a novel potential biomarker for FAP diagnosis. Collectively, our data show that silencing TTR liver synthesis in vivo can modulate TTR-induced pathology in the peripheral nervous system and highlight the potential of MMP-2 as a novel disease biomarker.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 47, November 2016, Pages 91-101
Journal: Neurobiology of Aging - Volume 47, November 2016, Pages 91-101
نویسندگان
Nádia Pereira Gonçalves, Paula Gonçalves, Joana Magalhães, Miguel Ventosa, Ana Varela Coelho, Maria João Saraiva,