TDP-43 (TAR DNA-binding protein 43) is an hnRNP (heterogeneous nuclear ribonucleoprotein) protein whose role in cellular processes has come to the forefront of neurodegeneration research after the observation that it is the main component of brain inclusions in ALS (amyotrophic lateral sclerosis) and FTLD (frontotemporal lobar degeneration) patients. Functionally, this aberrant aggregation and mislocalization implies that, in the affected neurons, transcripts regulated by TDP-43 may be altered. Since then, a considerable amount of data has been gathered on TDP-43 interactions and on the genes that are influenced by its absence or overexpression. At present, however, most of these data come from high-throughput searches, making it problematic to separate the direct effects of TDP-43 from secondary misregulations occurring at different levels of the gene expression process. Furthermore, our knowledge of the biochemistry of TDP-43, its RNA-binding characteristics, its nuclear and cytoplasmic targets, and the details of its interactions with other proteins is still incomplete. The understanding of these features could hold the key for uncovering TDP-43′s role in ALS and FTLD pathogenesis. We describe in the present paper our work on TDP-43 RNA binding, self-regulation and aggregation processes, and attempt to relate them to the neurodegenerative pathologies.
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Conference Article|
November 20 2013
The role of TDP-43 in the pathogenesis of ALS and FTLD
Marco Baralle;
Marco Baralle
*International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy
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Emanuele Buratti;
Emanuele Buratti
*International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy
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Francisco E. Baralle
Francisco E. Baralle
1
*International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy
1To whom correspondence should be addressed (emailbaralle@icgeb.org).
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Publisher: Portland Press Ltd
Received:
August 05 2013
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (6): 1536–1540.
Article history
Received:
August 05 2013
Citation
Marco Baralle, Emanuele Buratti, Francisco E. Baralle; The role of TDP-43 in the pathogenesis of ALS and FTLD. Biochem Soc Trans 1 December 2013; 41 (6): 1536–1540. doi: https://doi.org/10.1042/BST20130186
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