近期,EMBO J.上发表了题为“Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns”的文章,揭示了寡聚和RNA结合控制着TDP-43的稳定性、剪接功能、LLPS和亚细胞定位。作者着重提出,TDP-43的寡聚是由RNA...
当地时间2021年1月4日,来自加州大学圣地亚哥分校付向东和武汉大学周宇共同通讯在《Nature Structural & Molecular Biology》在线发表题为“TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS”的研究论文。文章阐述了氧化应激...
Here we find the features of TDP-43 fibrils that confer both reversibility and irreversibility by determining structures of two segments reported to be the pathogenic cores of human TDP-43 aggregation: SegA (residues 311–360), which forms three polymorphs, all with dagger-shaped folds; and Se...
2. B. S. Johnson et al., TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J. Biol. Chem. 284, 20329–20339 (2009). doi: 10.1074/jbc.M109.010264;pmid: 19465477 3. T. Arai et al., TDP-43 is a com...
The majority of TDP43 protein found in cytoplasmic inclusions is truncated, 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 ...
The immunoreactivity was distributed in selected anatomical areas, suggesting that TDP-43 aggregation might be involved in the AD pathogenesis.doi:10.1016/j.jalz.2008.05.2228Yamazaki, TsuneoNakasone, AiTakatama, MasamitsuLemere, CynthiaOkamoto, Koichi...
We have investigated the role of metabolic stress in protein aggregate formation analyzing how it is relevant to the co-aggregation observed between RGNEF and TDP-43 in motor neurons of ALS patients. Metabolic stress was able to induce formation of micronuclei, small nuclear fragments, in cultured...
These morphological changes may prime microglia near neurons with pTDP-43 aggregation for phagocytosis, in turn triggering immunophenotype changes; first, to a phagocytic state then to a dysfunctional one.BioMed CentralActa Neuropathologica CommunicationsMolly E. V. Swansonhttps://ror.org/03b94tp07...
2021年7月8日，刘聪课题组与方燕姗课题组再度展开合作，在Cell Research在线发表题为 Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation 的论文，发现分子伴侣Hsp70是维持TDP-43在细胞应激下的液-液相分离稳态、抑制TDP-43病理性聚集的关键分子，并进一步揭示了Hsp70...
In biochemical and cell culture models, TDP-43 has been identified as spontaneously aggregation prone [1, 27]. This propensity has been localised to a low-complexity domain in the C-terminal region that may play a role in RNA binding, granule formation, and/or liquid–liquid phase separation...