Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia1–3, two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-434,5. Here we
Methods of reducing FUS/TLS- or TDP-43-mediated neuronal cytotoxicity by UPF1Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of...
Aaron Gitler, Robert Farese Jr. and colleagues identify the RNA lariat debranching enzyme Dbr1 as a potent suppressor of TDP-43 toxicity in yeast. They further show that Dbr1 knockdown reduces TDP-43 toxicity in mammalian cells, identifying this enzyme a
[12]。疏水TMBIM蛋白在C端共享一个UPF0005一致基序,编码6或7个跨膜区 域,具有高度的遗传和功能守恒。TMBIM家族具有调节动物、植物和酵母的抗 应激进化保守机制等细胞保护功能。其中,BI1具有6个完全跨膜结构域,具有 [13] N端和C端胞质取向,以及C端重入环(图1.2)。 图1.2BI1分子结构示意图[13] BI1可通过...
(2014) Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther., 22, 20-28.Jackson, K. L. et al. Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 22, 20...
Methods of reducing TDP-43-mediated neuronal cytotoxicity in amyotrophic lateral sclerosis by a UPF1 polypeptide or polynucleotideNonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and...