کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8841586 | 1615026 | 2018 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacological disruption of the MID1/α4 interaction reduces mutant Huntingtin levels in primary neuronal cultures
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کلمات کلیدی
mTORCerebellar granule cell cultureglial fibrillary proteinS6KmHTThttMAP2CGNaCSFPP2AGFAPMid1 - mid1Huntington’s disease - بیماری هانتینگتونDIV - دیوdays in vitro - روز in vitroartificial cerebral spinal fluid - مایع مغزی نخاعی مغزیcerebellar granule neurons - نورونهای گرانشی مخچهHuntingtin - هانتینگتنmutant Huntingtin - هانتینگتن جهش یافتهmammalian target of rapamycin - هدف پستانداران رپامایسینprotein phosphatase 2A - پروتئین فسفاتاز 2AMicrotubule associated protein 2 - پروتئین مرتبط با میکروتوبول 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Pharmacological disruption of the MID1/α4 interaction reduces mutant Huntingtin levels in primary neuronal cultures Pharmacological disruption of the MID1/α4 interaction reduces mutant Huntingtin levels in primary neuronal cultures](/preview/png/8841586.png)
چکیده انگلیسی
Expression of mutant Huntingtin (HTT) protein is central to the pathophysiology of Huntington's Disease (HD). The E3 ubiquitin ligase MID1 appears to have a key role in facilitating translation of the mutant HTT mRNA suggesting that interference with the function of this complex could be an attractive therapeutic approach. Here we describe a peptide that is able to disrupt the interaction between MID1 and the α4 protein, a regulatory subunit of protein phosphatase 2A (PP2A). By fusing this peptide to a sequence from the HIV-TAT protein we demonstrate that the peptide can disrupt the interaction within cells and show that this results in a decrease in levels of ribosomal S6 phosphorylation and HTT expression in cultures of cerebellar granule neurones derived from HdhQ111/Q7 mice. This data serves to validate this pathway and paves the way for the discovery of small molecule inhibitors of this interaction as potential therapies for HD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 673, 23 April 2018, Pages 44-50
Journal: Neuroscience Letters - Volume 673, 23 April 2018, Pages 44-50
نویسندگان
Olivia Monteiro, Changwei Chen, Ryan Bingham, Argyrides Argyrou, Rachel Buxton, Christina Pancevac Jönsson, Emma Jones, Angela Bridges, Kelly Gatfield, Sybille KrauÃ, Jeremy Lambert, Rosamund Langston, Susann Schweiger, Iain Uings,