The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible...
Methods: To model the toxic effects of dominant ALS causing mutations, we have developed a transgenic C. elegans model of TDP-43 proteinopathies to study the cellular, molecular, and genetic underpinnings of TDP-43 mediated neurotoxicity. To model the consequences of TDP-43 loss of function we...
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 ...
Further analyses reveal that a TDP-43 knockdown-induced reduction in GluN2A contributes to synaptic loss. Our results show that loss of TDP-43 function underlies hippocampal and cortical synaptic degeneration in TDP-43 proteinopathies. 展开
43, we identified two major acetylated sites in the RNA-binding domains (Fig. 1f and Supplementary Fig. 4); Lys-145 in RRM1, which spans residues 105–169, and Lys-192 immediately adjacent to RRM2, which spans residues 194–257 (see Fig. 1g for schematic of TDP-43 acetylation sites)....
This study aimed to determine the role of TAR DNA binding protein-43 (TDP-43) in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and its underlying mechanisms. After ICH, expression of TDP-43 in the nucleus was significantly decreased, and its expression in the cytoplasm ...
ALS CHMP7 TDP-43 SMN complex SmD1 CRISPR screen RNA splicing Introduction Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons (MNs), resulting in the loss of motor function, respiratory failure,...
Although multipleCHCHD10mutations are associated with the spectrum of familial and sporadic frontotemporal dementia–amyotrophic lateral sclerosis (FTD–ALS) diseases, neither the normal function of endogenous CHCHD10 nor its role in the pathological milieu (that is, TDP-43 pathology) of FTD/ALS have...
These data strongly suggest that the pathological effect of TMEM106B’s polymorphism can be modulated by the interaction with TDP-43 in the brain. While the molecular mechanism underlying this interaction is currently unknown, one possibility is that TMEM106B facilitates the aggregation of TDP-43 ...
TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-...