在97%的ALS以及45%的额颞叶痴呆(FTLD)的病例中都发现TDP-43蛋白的不溶聚集物(aggregates)。在病理状态下,TDP-43从细胞核中清除,并在细胞质中进行错误定位,因此该蛋白在细胞核中的功能丧失(loss of function)以及在细胞质中的功能获得(gain of function)都...
为了研究这两个基因在FTD-ALS中的作用,美国梅奥医学中心Leonard Petrucelli/Yong-Jie Zhang团队(第一作者:邵炜博士)在Science发文题为Two FTD-ALS genes converge on the endosomal pathway to induce TDP-43 pathology and degeneration,TBK1在C9orf72...
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 ...
In addition, TDP43-containing aggregates are found in a significant number of patients with Alzheimer’s Disease (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 ...
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 ...
(TDP-43) aggregates in motor neurons [37]. Although TDP-43 aggregates are unlikely to be the ‘toxic species’ in ALS, they are surrogates for the presence of the aggregation pathway species thatarethought to be toxic; misfolded monomers and oligomers [38]. While motor neurons are central...
TDP-43 aggregates using the iGFP-NLSm cell-based system33,34. Whereas brain-derived seeds from cases 1 and 2 induced the formation of filamentous structures (Extended Data Fig.8c, arrows, and arrowheads), seeds from case 3 induced the formation of more round and compact aggregates (...
TDP-43Amyotrophic lateral sclerosis is a devastating neuromuscular degenerative disease characterized by a focal onset of motor neuron loss, followed by contiguous outward spreading of pathology including TAR DNA-binding protein of 43kDa (TDP-43) aggregates. Previous work suggests that TDP-43 can ...
(HIV-1) [2]. Subsequent study identified TDP-43 as a constituent of ubiquitinated insoluble aggregates found in the brains of individuals with frontotemporal lobar dementia (FTLD) [3], with more recent research establishing strong associations between TDP-43 and a range of neurodegenerative ...
Optineurin knock-out ( Optn -KO) mice, which have been generated by several researchers, exhibit motor neuron degeneration and TDP-43 aggregates, but no motor deficits. Motor dysfunction in ALS model mice is associated with TDP-43 in the spinal cord. We bred Optn -KO mice with TDP-43 ...