Dismantling of the second helical element in TDP-43 prion-like domain by methionine sulfoxidation impacts phase separation and amyloid formation, abrogates chaperone recognition and alters phosphorylation by casein kinase-1δ. Our results show that metamorphism in the post-translationally modified TDP-43 ...
Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J. Neurosci. 30, 10851–10859 (2010). Article CAS Google Scholar Wang, W. et al. The inhibition of TDP-43 mitochondrial localization blocks its ...
TDP-43 can localize to mitochondria, impair mitochondrial complexes and their functions of oxidation and phosphorylation, and lead to abnormal mitochondrial fission/fusion dynamics and transport. And TDP-43 triggers endoplasmic reticulum stress which results in cell death. The formation of cytosolic TDP...
and it has been shown that the C-terminal domain is intrinsically prone to aggregation. Mutations in the C-terminal region of the TDP43 gene have been associated with both ALS and FTLD, and are thought to facilitate ubiquitination and phosphorylation of the TDP43 protein, leading to the format...
3. Liu, Z. et al. Hsp27 chaperones FUS phase separation under the modulation of stress-induced phosphorylation. Nature structural & molecular biology 27, 363-372 (2020).4. Gu, J. et al. Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles. ...
cytoplasmicTDP-43aggregateswithubiquitinationorphosphorylation,andcellcyclesalsoalterate.Hereresearch progressontransgenicrodentmodelsmadebyTDP-43mutationoroverexpressionisreviewedtoexploremolecular mechanisms,pathologicalchangesandnewtherapiesforneurodegenerativedisease. Keywords:TDP-43;neurodegenerativedisease;ALS;animalmodel...
Alternatively, specific phosphorylation of hnRNPs may simply target them to SGs and due to TDP-43 association with these hnRNPs, it becomes localized to SGs where hnRNPs are present. Further support for an hnRNP-TDP-43 association was found in our model where we showed that JNK inhibition ...
polypeptide, where the antibody recognizes a full length, truncated or aggregated TDP-43, a full length human TDP-43 of a specific amino acid sequence, or a peptide comprising residues 390-414 of the specific amino acid sequence with phosphorylation of residues 409 and 410.SELECTED DRAWING: ...
such as ALS, FTLD, and AD, share a common prominent pathological feature known as TAR DNA-binding protein 43 (TDP-43) proteinopathy, which is usually characterized by the presence of aberrant phosphorylation, ubiquitination, cleavage and/or nuclear depletion of TDP-43 in neurons and glial cells...
the phosphorylation status of TDP-43 directly impacts its splicing function, prompting inquiry into the presence of abnormal phosphorylation of TDP-43 in tumor cells. While exogenous overexpression of TDP-43 can lead to elevated expression of the 35 kD isoform, which may exert cytotoxic effects on...