与此一致的是，D169G突变的TDP-43在人源细胞和果蝇模型中均引起比野生型TDP-43更强的细胞毒性和神经退化的表型。该研究提示，TDP-43核体的形成或许是细胞应激时的“第一防线”，其组装或功能异常可能与ALS的发生有重要关系。相关成果以Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via ...
Insoluble cytoplasmic aggregate formation of the RNA-binding protein TDP-43 is a major hallmark of neurodegenerative diseases including Amyotrophic Lateral Sclerosis. TDP-43 localizes predominantly in the nucleus, arranging itself into dynamic condensates through liquid鈥搇iquid phase separation (LLPS). ...
By contrast, LLPS of PrLD-less TDP-43 is promoted by salts, but only at acidic pH values lower than its pI of 5.59, as observed here (Fig.5C). At pH values close or higher than the pI of 5.59, LLPS of PrLD-less TDP-43 is inhibited, rather than promoted, as the salt concentr...
Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation Nat. Commun., 8 (2017), p. 45 View in ScopusGoogle Scholar Alberti and Hyman, 2021 S. Alberti, A.A. Hyman Biomolecular condensates at the nexus of cellular stress, protein aggregation ...
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 ...
在2020年7月9日以Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via paraspeckle lncRNA NEAT1-mediated liquid-liquid phase separation为题在线发表在Molecular Cell上的最新论文中。来中科院上海有机化学研究所生物与化学交叉研究中心方燕姗研究员课题组和刘聪研究员课题组合作揭示了不同类型...
14kAccesses 106Citations 18Altmetric Metrics Abstract Amyotrophic lateral sclerosis (ALS) was initially thought to be associated with oxidative stress when it was first linked to mutant superoxide dismutase 1 (SOD1). The subsequent discovery of ALS-linked genes functioning in RNA processing and proteos...
RNA granules such as P-bodies, stress granules and paraspeckles (also known as ‘membraneless organelles’) are formed in part through liquid–liquid phase separation (LLPS), a process similar to the de-mixing of oil and water and are vital for RNA metabolism [2••]. Numerous mutations...
The values of all relaxation parameters indicate that the protein is highly dynamic. B Secondary chemical shifts (ΔCα-ΔCβ) for MetO PLD309. C J-coupling assessment of the secondary structure propensities for MetO PLD309. Values around 4 Hz indicate α-helix formation, while values ...
Functional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation. Nature Communications, 8 (2017), pp. 1-15 Google Scholar Arai, 2014 T. Arai Significance and limitation of the pathological classification of TDP‐43 proteinopathy Neuropathology, 34 (2014)...