Intraneuronal aggregation of TDP-43 is seen in 97% of all amyotrophic lateral sclerosis cases and occurs by a poorly understood mechanism.

2013. 8. 9. · Background: TAR DNA-binding protein 43 (TDP-43) is a protein that is involved in the pathology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration

2018. 4. 13. · Phosphorylated TDP-43 (pTDP-43) aggregates in the axial skeletal muscle of patients with sporadic and familial amyotrophic lateral sclerosis Acta Neuropathol Commun.

Cytoplasmic aggregation of hyperphosphorylated TDP-43 (depicted by blue P) is a hallmark of TDP-43 proteinopathies and may result in cellular stress, aberrant stress granule formation, mitochondrial dysfunction, reduced autophagy and dysfunction of proteosomal processes.

In , Liu and collaborators developed peptides targeting TDP-43-CTD to decrease TDP-43 aggregation and reduce subsequent toxicity in cells.

2012. 6. 26. · Moreover, TDP-43 is an aggregation-prone protein and, given the role of toxic protein aggregates in neurodegeneration, a toxic gain-of-function mechanism is another

Mutations that disrupt TDP-43 RNA binding may contribute to pathogenic mislocalization and aggregation in ALS and FTLD-TDP [31].

The strong role of TPD-43 in the pathophysiology of ALS points to TDP-43 as a cogent pharmacological target for disease modification. Aquinnah Pharmaceuticals has licensed 10 lead compounds that inhibit TDP-43 and SG aggregation that were identified in a high throughput screen performed in the laboratory of Dr. Benjamin Wolozin (Boston

The formation of TDP-43 inclusions within micronuclei induced by metabolic stress is a novel mechanism of protein aggregate formation which may 

2020. 9. 2. · Poly(GR) directly accelerates and enhances TDP-43 aggregation. (A) TDP-43–MBP (5 μM) was incubated with buffer, 2 μM poly(GR), or 2 μM poly(GA) in the presence or absence of TEV protease (1 μg/ml).Aggregation was assessed by turbidity measured at an absorbance of 395 nm. Values are normalized mean ±SEM (n = 6).(B) Quantification of the area under the

TDP-43 forms aggregates inside micronuclei Besides the enrichment of TDP-43 and RGNEF in micronuclei formed after metabolic stress, we noted the formation of TDP-43 protein inclusions inside these