TDP-43: gumming up neurons through protein-protein and protein-RNA interactions |
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Authors: | Buratti Emanuele Baralle Francisco E |
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Institution: | International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy. |
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Abstract: | Since the discovery that 43 kDa TAR DNA binding protein (TDP-43) is involved in neurodegeneration, studies of this protein have focused on the global effects of TDP-43 expression modulation on cell metabolism and survival. The major difficulty with these global searches, which can yield hundreds to thousands of variations in gene expression level and/or mRNA isoforms, is our limited ability to separate specific TDP-43 effects from secondary dysregulations occurring at the gene expression and various mRNA processing steps. In this review, we focus on two biochemical properties of TDP-43: its ability to bind RNA and its protein-protein interactions. In particular, we overview how these two properties may affect potentially very important processes for the pathology, from the autoregulation of TDP-43 to aggregation in the cytoplasmic/nuclear compartments. |
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