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

Chimia (Aarau). 2019 May 29;73(6):380-390. doi: 10.2533/chimia.2019.380.


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.

Publication types

  • Review

MeSH terms

  • Humans
  • Neurodegenerative Diseases*
  • TDP-43 Proteinopathies