病理TDP-43聚集体由全长蛋白质和异常切割的C末端片段(CTF)组成18 ~ 35 kDa,聚集体不溶于去污剂Sarkosyl并含有异常的翻译后修饰,包括泛素化和磷酸化。聚集体的电子显微镜(EM)成像显示它们是颗粒丝状且不分枝,直径为10 ~ 15 nm。聚集体的...
免疫印迹证实,提取的聚集体由全长TDP-43和CTFs组成,并在S409和S410位点磷酸化(pS409/S410)(图3b,扩展数据图3c),与先前在ALS和FTLD12中观察到的结果一致。免疫金阴性染色电镜(immune -EM)显示TDP-43聚集体呈螺旋状投影宽度为10-15 nm的细丝(图3d,扩展数据图3d),类似于从FTLD6患者中提取的聚集TDP-43,以及AL...
To identify novel causes of familial neurodegenerative diseases, we extended our previous studies of TAR DNA-binding protein 43 (TDP-43) proteinopathies to investigate TDP-43 as a candidate gene in familial cases of motor neuron disease. Sequencing of the TDP-43 gene led to the identification ...
与预测的一致,把G314残基改变为缬氨酸破坏了A315E-TDP-43多肽纤维的形成,如EM或原子力显微镜所示,具体请参阅图3。 实施例二: FTLD-TDP大脑样本中TDP-43免疫反应性纤维的检测 为了检测TDP-43在体外是否形成纤维状聚合物,我们使用免疫电子显微镜(IEM)来检测病理确诊为FTLD-TDP患者的大脑组织。如图3和4所示,IEM使用...
S. Eisenberg团队（上海交通大学曹骎等为第一作者）在Nature 在线发表题为“Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43”的研究论文，该研究从四名患者的大脑中提取了淀粉样蛋白原纤维，代表了五个 FTLD-TDP 亚类中的四个，并通过冷冻电子显微镜 (cryo-EM) 确定了它们的近原子...
Vanden Berghe P, Verfaillie C, Van Den Bosch L, Van Damme P. HDAC6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. EMBO J. 2021 Apr 1;40(7):e106177...
Functional TDP-43 aggregates form reversible, transient species such as nuclear bodies, stress granules, and myo-granules. Pathogenic, irreversible TDP-43 aggregates form in amyotrophic lateral sclerosis and other neurodegenerative conditions. Here we find the features of TDP-43 fibrils that confer ...
右侧面板中的定量显示在薄层EM切片(50nm厚)中,每平方μm线粒体的平均数量的TDP-43金颗粒。箭头指向免疫金标记的TDP-43。等量的10μg蛋白质加载至所有的免疫印迹中。数据为三个重复的独立试验的平均值±s.e.m。统计学:单因素方差分析(ANOVA),然后进行Tukey多重比较检验。*P<0.05,**P<0.01和***P<0.01。 图...
[1] Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017 Oct 5;3:17071. [2] Gregory, J.M., Fagegaltier, D., Phatnani, H. et al. Genetics of Amyotrophic Later...
[1] Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017 Oct 5;3:17071. [2] Gregory, J.M., Fagegaltier, D., Phatnani, H. et al. Genetics of Amyotrophic Later...