In particular, TDP43, implicated in Amyotrophic Lateral Sclerosis (ALS), partitions dynamically between two distinct types of aggregates: stress granule and a previously unknown non-dynamic (solid-like) inclusion at the ER exit sites (ERES). TDP43-ERES co-aggregation is induced by diverse ...
g, Stress-granule formation in multinucleated myotubes derived from C2C12 cells. Immunofluorescence using antibodies against stress-granule proteins, G3BP1 and PABP1, after NaAsO2 treatment or control conditions for 60 min. n = 3 independent experiments, each showing similar results. Zoom, ...
McDonald KK, Aulas A, Destroismaisons L, Pickles S, Beleac E, Camu W, Rouleau GA, Vande Velde C (2011) TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Hum Mol Genet 20:1400–1410. doi:10.1093/hmg/ddr021 51. ...
In contrast, a second mutation TDP-43(D169G) does not impact this pathway. Thus, mutations in TDP-43 are mechanistically divergent. Finally, the cellular function of TDP-43 extends beyond splicing and places TDP-43 as a participant of the central cellular response to stress and an active ...
L., Davies, B. et al. (2019). Single-copy expression of an amyotrophic lateral sclerosis-linked TDP-43 mutation (M337V) in BAC transgenic mice leads to altered stress granule dynamics and progressive motor dysfunction. Neurobiol. Dis. 121, 148-162....
Small molecules could therapeutically prevent cytoplasmic aggregations of TDP-43 by post-translational modifications through (i) protease kinase inhibitors and inhibiting TDP-43 hyperphosphorylation, (ii) inhibiting solid state stress granule formations, and (iii) regulating protein homeostasis pathways UPS, ...
TDP-43 is involved in multiple cellular functions, such as regulation of RNA metabolism, mRNA transport, and stress granule formation. It also plays a pivotal role in the regulation of transcription and mRNA splicing [28]. TDP-43 also appears to be critical for the development of neuronal ...
(transactive response DNA-binding protein-43)在细胞质中形成包涵体是ALS的特征性病理标志之一.病理性TDP-43通过影响细胞内多 种生理过程介导了神经退变的发生,如TDP-43可损害线粒体功能,引发内质网应激(endoplasmic reticulum stress,ER stress),TDP-43的病理性聚集与应激颗粒(stress granule,SG)有密切关系, TDP-...
(2011) TAR DNA-binding protein 43 (TDP-43) regulates stress granule dynamics via differential regulation of G3BP and TIA-1. Hum Mol Genet 20: 1400–1410. [23] Abhyankar MM, Urekar C, Reddi PP (2007) A novel CpG-free vertebrate insulator silences the testis-specific SP-10 gene in ...
JNK: c-JUN N-terminal kinase SG: stress granule SOD: superoxide dismutase TDP-43: TARDP-binding protein 43.References King AE, Dickson TC, Blizzard CA, Woodhouse A, Foster SS, Chung RS, Vickers JC: Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology. Neurobiol Aging....