Academic Journal
Symmetric dimethylation of poly-GR correlates with disease duration in C9orf72 FTLD and ALS and reduces poly-GR phase separation and toxicity
| العنوان: | Symmetric dimethylation of poly-GR correlates with disease duration in C9orf72 FTLD and ALS and reduces poly-GR phase separation and toxicity |
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| المؤلفون: | Gittings, LM, Boeynaems, S, Lightwood, D, Clargo, A, Topia, S, Nakayama, L, Troakes, C, Mann, DMA, Gitler, AD, Lashley, T, Isaacs, AM |
| المصدر: | Acta Neuropathologica (2019) (In press). |
| سنة النشر: | 2019 |
| المجموعة: | University College London: UCL Discovery |
| الوصف: | A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Pathologically, patients are characterised by TDP-43 pathology and distinct inclusions containing dipeptide repeat proteins (DPRs) that are produced by repeat associated non-ATG initiated translation of the repeat expansion. This produces five different DPRs: poly-GA, poly-GR poly-PR poly-AP and poly-GP. Poly-GR and poly-PR have been shown to be highly toxic in in vitro and in vivo models, but the mechanisms are not entirely clear [1]. We investigated whether methylation of arginine residues in poly-GR (which is much more abundant than poly-PR) contributes to disease pathogenesis. Three types of arginine methylation can occur, monomethylarginine (MMA), or dimethylarginine in a symmetric (SDMA) or asymmetric (ADMA) confirmation. ADMA is the most prevalent modification with MMA and SDMA occurring at approximately 20–50% that of ADMA [2]. The importance of arginine methylation in FTD and ALS has recently come to light as methylation of arginine residues within the FTD/ALS-linked proteins FUS and hnRNPA2 is an important regulator of their liquid–liquid phase transition [7]. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/10088152/1/Isaacs_Symmetric%20dimethylation%20of%20poly-GR%20correlates%20with%20disease%20duration%20in%20C9orf72%20FTLD%20and%20ALS%20and%20reduces%20poly-GR%20phase%20separation%20and%20toxicity_AOP.pdf; https://discovery.ucl.ac.uk/id/eprint/10088152/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/10088152/1/Isaacs_Symmetric%20dimethylation%20of%20poly-GR%20correlates%20with%20disease%20duration%20in%20C9orf72%20FTLD%20and%20ALS%20and%20reduces%20poly-GR%20phase%20separation%20and%20toxicity_AOP.pdf https://discovery.ucl.ac.uk/id/eprint/10088152/ |
| Rights: | open |
| رقم الانضمام: | edsbas.39A22BDB |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |