Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration

By Eddie B. Lee, V. Lee, John Q. Trojanowski. Nature Reviews Neuroscience, 2011

648 citations recorded by the source corpus.

RNA-binding proteins, and in particular TAR DNA-binding protein 43 (TDP43), are central to the pathogenesis of motor neuron diseases and related neurodegenerative disorders. Studies on human tissue have implicated several possible mechanisms of disease and experimental studies are now attempting to determine whether TDP43-mediated neurodegeneration results from a gain or a loss of function of the protein. In addition, the distinct possibility of pleotropic or combined effects — in which gains of toxic properties and losses of normal TDP43 functions act together — needs to be considered.

Subfields: Genetics, Neurology

View Paper: https://www.semanticscholar.org/paper/af7f616efec42e055ac7c443a7c508cde73bc33a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Elizabeth T. Cirulli
2. Robert H. Brown
3. J. Shorter
4. Thomas Tuschl
5. Aaron Gitler
6. Oliver D. King
7. Gregory M. Cooper
8. Richard M. Myers

In Neurology

1. V. Lee
2. John Q. Trojanowski
3. K. Del Tredici
4. H. Braak
5. Oliver D. King
6. J. Shorter
7. Robert H. Brown
8. Aaron Gitler

Citations in the corpus

• Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways (2015, positive): “Remarkably, a hallmark of motor neuron pathology in >95% of sporadic and familial ALS patients is the formation of TARDBP inclusions, suggesting that defects in ribostasis is a common feature of the disease (5, 49).”
• The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease (2012, background): “Aggregated C-terminal fragments of TDP-43 containing the prion-like region are biochemical signatures of ALS (Lee et al., 2011; Neumann et al., 2006).”
• Stages of pTDP‐43 pathology in amyotrophic lateral sclerosis (2013, background): “TDP-43 is a highly conserved and widely expressed RNA-binding protein that is a member of the heterogeneous nuclear ribonucleoprotein family of proteins.(3) The defining”
• Impact of multiple pathologies on the threshold for clinically overt dementia (2017, background): “TDP-43 is related to neuronal loss, which may arise due to deleterious loss of TDP-43 from the nucleus [76].”
• A census of human RNA-binding proteins (2014, background): “sclerosis, a motor neuron disease leading to muscle atrophy (Anthony and Gallo, 2010; LagierTourenne et al., 2010; Lee et al., 2012; Ling et al., 2013).”