TDP-43 pathology-positive subjects are 10 times more likely to be cognitively impaired at death compared to TDP-43-pathology negative cases (Josephs et al., ). Nevertheless this review will focus on the loss-of-function aspect of the protein. Although how this essential RNA-binding protein contributes to the pathogenesis of ALS and FTD

Nov 01,  · Trans-activation response DNA-binding protein of 43 kDa (TDP-43), encoded by the gene on chromosome 1, is a major component of tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS; see Glossary) and frontotemporal lobar degeneration (FTLD) linked to TDP-43 pathology (FTLD-TDP) [1].

Dec 20,  · Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking,

hypothesis, which postulates that mutant TDP-43 causes neurodegeneration by a loss of function, and in addition, by exerting a dominant-negative effect on the wild-type TDP-43 allele. Furthermore, I will discuss how a loss of function can cause neurodegeneration in patients where TDP-43 is not mutated, review the literature in model

TDP-43 protein is ubiquitously expressed in all cells of the body, although at differing levels and in several organs, its expression can vary substantially during development. For example, TDP-43 protein expression is significantly reduced in the brain and spinal cord during the maturation of the CNS.

This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration. http://creativecommons.org/licenses/by-nc/4./

Dec 17,  · TDP-43 structure and effect on localization is paralleled by many RNA-binding proteins and this review serves as an example of how structure may be modulated by

Current studies show that the pathophysiological mechanism of TDP-43 in neurodegeneration is very complex. In this review, we describe the structure of TDP-43, its main physiological functions, the possible pathogenesis and how TDP-43 provides a new pathway to treat neurodegenerative diseases. Keywords:

Thus, unraveling the molecular mechanisms of the TDP-43 pathology seems central to the ALS therapeutics, hence, we comprehensively review the current understanding of the TDP-43's pathology in ALS. We discuss the roles of TDP-43's mutations, its cytoplasmic mis-localization and aberrant post-translational modifications in ALS.

Our results demonstrate that the presence of TDP-43 in the hypoglossal nucleus discriminates patients with amyotrophic lateral sclerosis with an accuracy of 98%. The severity of TDP-43 deposited in the anterior cingulate cortex identifies patients with behavioural variant frontotemporal dementia with an accuracy of 99%.

Read a post-publication review of TDP-43 dysfunction results in R-loop accumulation and DNA replication defects on Publons. They clearly based their research question about the role of TDP-43 in regulating R-loops on previously published articles. 3) They wrote a cohesive introduction introducing the broader topic of R-loops and their role