不过,通过ALS病理研究可发现,TDP-43蛋白异常是该病患者病变区神经元普遍发生的现象。神经元是大脑中上传下达的基本单元,也是神经退行性疾病发生与进展的关键单元。据报道,相当多的神经退行性疾病患者——97%的ALS、45%的额颞叶变性痴呆...
TDP-43在细胞内主要参与RNA代谢调控,包括转录、翻译、mRNA前体剪接等过程【1, 2】。以 TDP-43 细胞质聚集和核丢失为特征的 TDP-43 蛋白病理变化是多种神经退行性疾病的常见病理特征,包括肌萎缩侧索硬化症(ALS)、额颞叶变性(FTLD...
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通过结合TDP-43上保守的聚集核心区域行使该调控功能的分子机制。该
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 ...
Despite intensive research, the mechanisms behind protein aggregate formation in ALS remains unclear. 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...
The cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD). However, the composition of aggregates and their contribution to the disease process...
相关研究结果近期发表在Science Translational Medicine期刊上，论文标题为“C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy”。特别地，毒性的poly(GR)蛋白以RNA不依赖的方式介导全长TDP-43的封存，从而诱导细胞质TDP-43包涵体形成。此外，在GFP-(GR)200小鼠中，poly(GR)引起核质转运因子（nucleocytoplasmic...
TDP-43 aggregation in TDP-43Q331K mice and dramatic- ally increases the toxicity such that 50 % of the mice are dead by 8 weeks. Assessment of the single transgenic an- imals used in this study have suggested that Q331K mu- tant TDP-43 has a greater tendency to aggregate in the ...
(AD) and other neuromuscular disorders. 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 ...
Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced plurip