کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6264315 | 1613977 | 2012 | 12 صفحه PDF | دانلود رایگان |

The overview of TDP 43 functions immediately disclose a number of open questions regarding its pathological role. The formation of TDP-43 aggregates is one of the major distinguishing features of TDP-43 proteinopathies, especially in patients affected by Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar degeneration (FTLD). At the moment, however, very little is known regarding the biological processes that underlie TDP-43 aggregation and, most importantly, its potential consequences on cellular metabolism. For these reasons, it is particularly important to further investigate this process in order to gain a better understanding of the pathology and to develop novel therapeutic effectors. In this report, we focus on a series of missense mutations associated with disease in the 342-366 region of this protein to examine their ability to affect RNA splicing regulation and to induce aggregate formation. In particular, aggregate formation was assessed in a novel system capable of inducing TDP-43 aggregation in experimental cell lines and primary neuronal cultures. The results of this analysis showed that the presence of two of these missense mutations in the 342-366 region (G348V and N352S) could differentially affect the levels and appearance of TDP-43 aggregation with respect to the wild-type protein.This article is part of a Special Issue entitled RNA-Binding Proteins.
224Highlights⺠TDP-43 is the main component of neuronal inclusions in ALS/FTLD patients. ⺠We found that its Q/N-rich region (residues 342-366) is involved in aggregation. ⺠Inserting this sequence as a repeated unit (12X-Q/N) can induce this phenomenon. ⺠Disease-associated mutations in this region can enhance aggregation of TDP-43.
Journal: Brain Research - Volume 1462, 26 June 2012, Pages 139-150