2021. 10. 25. · Dendritic spine loss induced by TDP-43 knockdown is rescued by wild-type TDP-43, but not ALS/FTLD-associated mutants, suggesting a common TDP-43 functional deficiency

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2011. 4. 1. · TDP-43 is an evolutionarily conserved ubiquitously expressed DNA/RNA-binding protein. Although recent studies have shown its association with a variety of neurodegenerative disorders, the function of TDP-43 remains poorly understood. Here we address TDP-43 function using spermatogenesis as a model system.

TDP-43 is a protein that regulates gene expression. TDP-43 aggregation and depletion from cell nucleus are found in ALS. Therefore, TDP-43 may cause neurodegeneration by generating toxicity from its aggregation or by a loss of its function. Our experiments test the consequence of a partial loss of TDP-43 function in mice.

An acetylation switch controls TDP-43 function and aggregation propensity TDP-43 pathology is a disease hallmark that characterizes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Although a critical role for TDP-43 as an RNA-binding protein has emerged, the regulation of TDP-43 function is poorly understood.

TDP-43 binds both mRNA and DNA, thereby regulating mRNA splicing, stability and translation as well as gene transcription. Although early in 

Our results show that a similar phenotypic outcome results from increased inclusion of Sort1 exon 17b caused by abnormal TDP-43 function, leading to production of a soluble form of Sortilin that diverts trafficking of proBDNF away from the regulated secretory pathway, thereby impairing activity-dependent BDNF secretion. A disease-associated

TDP-43 aggregation and redistribution have been recognised as a hallmark of amyotrophic lateral sclerosis, frontotemporal dementia and other neurological disorders. While TDP-43 has been studied extensively in neuronal tissues, TDP-43 inclusions have also been described in the muscle of inclusion body myositis patients, highlighting the need to understand the role of TDP-43 beyond the central

When TDP-43 function is lost, these cryptic exons stay incorporated and often introduce frameshift or premature stop codons, targeting aberrant transcripts for 

2022. 5. 2. · The pathogenesis of TDP-43 includes the theory of function gain and the theory of function loss [].According to the theory of function gain, overexpression or mutation of TARDBP and mislocalization of TDP-43 can induce toxicity, resulting in neuronal damage and axonal damage (Fig. 2) [32, 33].Neuropathology is characterized by the formation of cytoplasmic TDP

The scheme illustrates that TDP-43 functions normally as dimer or oligomer conformers in the nuclear compartment. However, upon translocation to the cytoplasm, truncation of TDP-43 promotes aggregation (gain-of-function).