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 

2019. 1. 29. · Abnormal TDP-43 function culminate in impaired secretion of neurotrophin BDNF, whose restoration is sufficient to rescue major disease phenotypes caused by aberrant TDP-43 activity. Knockdown, aggregation or disease-associated mutation of TDP-43 impair intracellular sorting and activity-dependent secretion of the neurotrophin brain-derived neurotrophic factor

2016. 9. 12. · TDP-43 loss of function as seen in ALS and FTLD inhibits trafficking of recycling endosomes in rat and human neurons. Impaired recycling to the cell surface inhibits trophic signaling of ErbB4 and other receptors. TDP-43 knockdown inhibits motility of recycling endosomes in dendrites by inducing the expression of VPS4B, an ESCRT disassembly factor,

1 As TDP-43 shuttles between nucleus and cytoplasm, it engages in diverse functions within both compartments (figure 1B). In the nucleus, TDP-43 regulates many 

Loss of TDP-43 function underlies hippocampal and cortical synaptic deficits in TDP-43 proteinopathies Loss of TDP-43 function underlies hippocampal and cortical synaptic deficits in TDP-43 proteinopathies Mol Psychiatry. Oct 25. doi: 10.1038/s41380-021-01346-. Online ahead of print. Authors

2. Genetics, protein structures, and biological functions of TDP-43. TDP-43 was identified from a genomic screen for novel transcriptional inactivators that bind to the TAR-DNA element of the HIV-1 virus, where it functions as a transcriptional repressor [].The human TDP-43 gene, which is located on chromosome 1 and contains 6 exons, is alternatively spliced to generate at least

and confers TDP-43 the ability to undergo LLPS both in vitro (33) and in cells (35); intermolecular interactions mediated by the folded N-terminal domain further enhance TDP-43 LLPS and function (21). In addition to the tandem RRMs, the splicing function of TDP-43 also depends on the N- and C-terminal domains (21, 36 -40).

Phosphorylated TDP-43 potentiates a number of neurotoxic effects including reduced liquid–liquid phase separation dynamicity, changes in 

Nuclear TDP-43 depletion could be an early pathogenic event, possibly preceding its cytoplasmic aggregation, and while promising therapeutic options for reducing TDP-43 aggregation mediated toxicity are being developed, further effort is needed to clarify the different contributions of toxic gain of function and nuclear loss of function of TDP

TDP-43 also acts as the transcriptional repressor and/or insulation regulator for the spatiotemporal regulation of the ACRV1 (SP-10) gene [140, 141]. TDP-43 

Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats ( ) Jianbin Tong et al. EMBO JOURNAL Premature death of TDP-43 (A315T) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis

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 

By changing HSPB1 and TDP-43's concentrations in vitro, the researchers found that the former ushered the latter into liquid droplets, but prevented the droplets from hardening into gels or solids. The chaperone also blocked TDP-43 from twisting into amyloid fibrils. In cells, most of the TDP-43-containing liquid droplets dissipated after the

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.

TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous

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

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.

The two major RNA Binding Proteins involved in Amyotrophic Lateral Sclerosisi and Frontotemporal Dementia are TDP-43 and FUST/TLS. Both proteins are involved in regulating all aspects of RNA and RNA life cycle within neurons, from transcription, processing, and transport/stability to the formation of cytoplasmic and nuclear stress granules.

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).

Transactive response DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in transcriptional regulation and RNA processing. It is linked.