Most importantly, the expression of hnRNP A1/A2 and PTB/nPTB is significantly altered in patients with frontotemporal dementia with TDP-43-positive inclusions (FTLD-TDP), indicating that perturbations in RNA metabolism and processing in FTLD-TDP are not exclusively driven by a loss of TDP-43 function.

although tdp-43 was originally described to harbor transcription repressor activity ( 12 ), the functions of tdp-43 has since been expanded to include a wide range of biological processes ( 7, 13 - 15 ), including biogenesis and processing of coding and noncoding rnas ( 7, 13 - 15 ), mrna transport ( 16 ), translation ( 17, 18 ), mitochondrial

Whether ALS/FTD is caused by loss of TDP-43 nuclear function (LOF) or newly gained cytoplasmic function (GOF) remains unknown. In LCDmut mice, TDP-43 

TDP-43 has diverse cellular roles in regulating RNA splicing and RNA stability as well as other gene regulatory functions 3, 4, 5. High-throughput sequencing approaches have shown that TDP-43 binds

2011. 11. 1. · Indeed, using a mouse-specific TDP-43 antibody, Igaz et al. demonstrated endogenous mouse TDP-43 clearing in either wild-type TDP-43 or TDP-43-ΔNLS expressing

2014. 2. 1. · TDP-43 is normally expressed in the nucleus of neurons where its most important function is to regulate RNA processing, including mRNA splicing, mainly by binding to UG-rich intronic regions 11, 12.However, in the ALS–FTD patients, TDP-43-positive inclusions are typically found in the neuronal cytoplasm and accompanied by a loss of the normal nuclear expression

2021. 10. 25. · TDP-43 proteinopathy is linked to neurodegenerative diseases that feature synaptic loss in the cortex and hippocampus, although it remains unclear how TDP-43 regulates mature synapses. We report that, in adult mouse hippocampus, TDP-43 knockdown, but not overexpression, induces robust structural and functional damage to excitatory synapses,

Thus, denervation of NMJs and dysregulated synaptic function may be related to declining neuronal function in ALS and FTLD. TDP-43 

2020. 8. 15. · TDP-43 function, dysfunction, and aggregation. TDP-43 is a highly conserved and essential DNA/RNA binding protein belonging to the heterogenous ribonucleoprotein family

These results suggest that functions associated with RRM-1, such as (UG)n RNA binding, confer TDP-43 mobility in the nucleus. The function of RRM-2 remains 

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