The role of TDP-43 in the pathogenesis of ALS and FTLD.

Abstract:

: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.

journal_name

Biochem Soc Trans

authors

Baralle M,Buratti E,Baralle FE

doi

10.1042/BST20130186

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

1536-40

issue

6

eissn

0300-5127

issn

1470-8752

pii

BST20130186

journal_volume

41

pub_type

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