C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins

  title={C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins},
  author={Yong-Jie Zhang and Tania F. Gendron and Jonathan C. Grima and Hiroki Sasaguri and Karen R. Jansen-West and Ya-fei Xu and Rebecca B. Katzman and Jennifer M Gass and Melissa E. Murray and Mitsuru Shinohara and Wen-lang Lin and Aliesha Garrett and Jeannette N Stankowski and Lillian M. Daughrity and Jimei Tong and Emilie A. Perkerson and Mei Y Yue and Jeannie Chew and Monica Castanedes-Casey and Aishe Kurti and Zizhao Selina Wang and Amanda M. Liesinger and Jeremy D. Baker and Jie Jiang and Clotilde Lagier-Tourenne and Dieter Edbauer and Don W Cleveland and Rosa Rademakers and Kevin B. Boylan and Guojun Bu and Christopher D Link and Chad A Dickey and Jeffrey D Rothstein and Dennis W. Dickson and John D Fryer and Leonard Petrucelli},
  journal={Nature Neuroscience},
Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation. HR23… CONTINUE READING