Structural Transition, Function and Dysfunction of TDP-43 in Neurodegenerative Diseases

Authors

  • Tariq Afroz
  • Manuela Pérez-Berlanga
  • Magdalini Polymenidou

DOI:

https://doi.org/10.2533/chimia.2019.380

PMID:

31118120

Keywords:

Als, Ftd, Neurodegenerative diseases, Protein misfolding, Protein aggregation, Rna metabolism, Tdp-43, Tdp-43 proteinopathies

Abstract

Altered cellular localization and pathologic aggregation of RNA binding proteins (RPBs) containing low complexity regions (LCRs) is a hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the importance of RBPs in maintaining a healthy RNA homeostasis, a common mechanism in disease progression is the loss of RNA-related cellular functions. In this review, we summarize and discuss the knowledge gained in the recent years on the molecular mechanisms of TDP-43 proteinopathies that comprise a set of neurodegenerative diseases characterized by the mislocalization and aggregation of the RNA-binding protein TDP-43. Based on biophysical, biochemical and in vivo data, we highlight pathways that are misregulated early in disease and contribute to its progression, thereby representing attractive therapeutic targets.

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Published

2019-05-29

Issue

Section

Scientific Articles

How to Cite

[1]
T. Afroz, M. Pérez-Berlanga, M. Polymenidou, Chimia 2019, 73, 380, DOI: 10.2533/chimia.2019.380.