Amyotrophic Lateral Sclerosis-associated GGGGCC repeat expansion promotes Tau phosphorylation and toxicity
Amyotrophic Lateral Sclerosis-associated GGGGCC repeat expansion promotes Tau phosphorylation and toxicity
复制标题
肌萎缩侧索硬化症相关的 GGGGCC 重复扩增促进 Tau 磷酸化和毒性
DOI：
10.1016/j.nbd.2019.104493
复制
发表时间：
2019-10-01
影响因子：
6.1
通讯作者：
Duan, Ranhui
中科院分区：
文献类型：
--
作者：
He, Hua;Huang, Wen;Duan, Ranhui
Microtubule-associated protein Tau (MAPT) and GGGGCC (G(4)C(2)) repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) are the major known genetic causes of frontotemporal dementia (FTD) and other neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS). Although expanded G(4)C(2) repeats and Tau traditionally are associated with different clinical presentations, pathological and genetic studies have suggested a strong association between them. Here we demonstrate a strong genetic interaction between expanded G(4)C(2) repeats and Tau. We found that co-expression of expanded G(4)C(2) repeats and Tau could produce a synergistic deterioration of rough eyes, motor function, life span and neuromuscular junction morphological abnormalities in Drosophila. Mechanistically, compared with the normal allele containing (G(4)C(2))(3) repeats, the (G(4)C(2))(30) allele increased Tau phosphorylation levels and promoted Tau R406W aggregation. These results together suggest a potential crosstalk between expanded G(4)C(2) repeats and Tau in modulating neurodegeneration.
