Our study addressed the impact of selected ALS-associated genes on TDP-43 aggregation behavior in wild-type and aggregation prone TDP-43 in vitro cell 

accordingly, in the present study, we report that not only exogenous but also endogenous rns can trigger tdp-43 aggregation via s-nitrosylation and consequent disulfide bond formation; in models of ftd and als, we identify endogenous sno-tdp-43 formation as a critical effector of pathological signaling, leading to its aggregation, altered

As discussed in Section 1, the significance of TDP-43 aggregation in disease is still a very debated subject.

The TDP-43 assays are SIMOA® assay kits for the measurement of the TAR DNA binding protein of 43 kDa in serum and human plasma.

In ALS and FTLD-U, aggregated, ubiquitinated, and N-terminally truncated TDP-43 can be isolated from brain tissue rich in neuronal and glial cytoplasmic inclusions. The loss of TDP-43 function resulting from inappropriate cleavage, translocation from the nucleus, or its sequestration into inclusions could play important roles in neurodegeneration.

To determine whether the insulin/IGF-1 signaling also modulates the aggregation of TDP-43 in a mammalian system, we used the aforementioned cell-based model of TDP-43 aggregation. Human HEK293T cells were transiently transfected with Myc-tagged human TDP-43 carrying Q331K, a mutation linked to familial ALS, with or without an small hairpin RNA (shRNA)

TAR DNA binding protein (TDP-43) has been found to be a major component of inclusion bodies in motor neurons of ALS patients. Inclusion bodies are protein aggregates considered a pathological hallmark of neurodegeneration. Our group and eight independent research groups screened TDP-43 for mutations.

The major aggregating protein in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the RNA-binding protein TDP-43, 

2019. 3. 8. · TAR DNA-binding protein 43 (TDP-43) is a nucleic acid–binding protein, and its aggregation represents the defining pathology in amyotrophic lateral sclerosis (ALS) and related proteinopathies. Recent studies implicate cytoplasmic stress granules (SGs) as hubs that may facilitate TDP-43 aggregation. Here, using cellular fractionation, biochemical analyses, and

SG assembly can trigger TDP-43 aggregation . We and others have shown that poly(GR) promotes the aggregation of recombinant TDP-43, colocalizes with TDP-43 in SGs in cultured cells, and coaggregates with TDP-43 in postmortem tissue from patients with c9ALS/FTD (11, 14, 27). Together, these findings suggest that poly(GR) contributes to c9ALS/FTD

2022. 9. 6. · Dysfunction and aggregation of the RNA-binding protein, TDP-43, is the unifying hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mechanisms and relative contributions of concurrent TDP-43 nuclear depletion, cytoplasmic accumulation, and post-translational modification to neurodegeneration remain unresolved.