@article{53a943e6df1c464fb755d796e15cccca,
title = "UPF1 reduces C9orf72 HRE-induced neurotoxicity in the absence of nonsense-mediated decay dysfunction",
abstract = "Zaepfel et al. show that UPF1 is neuroprotective in the context of C9-ALS. This neuroprotection is observed in multiple in vitro and in vivo models of C9-ALS. UPF1 mitigates toxicity independently of its role in nonsense-mediated decay but is dependent on its known RNA-binding and helicase activity.",
keywords = "C9ORF72, UPF1, amyotrophic lateral sclerosis, frontotemporal dementia, induced pluripotent cells, neurons, neurotoxicity, nonsense-mediated decay",
author = "Zaepfel, {Benjamin L.} and Zhe Zhang and Kirstin Maulding and Coyne, {Alyssa N.} and Weiwei Cheng and Hayes, {Lindsey R.} and Lloyd, {Thomas E.} and Shuying Sun and Rothstein, {Jeffrey D.}",
note = "Funding Information: We thank the ALS patients and their families for essential contributions to this research and the Target ALS Human Postmortem Tissue Core for providing postmortem human tissue. We thank Xiaopei Tang and Weibo Zhou for expert assistance with iPSC differentiations and Lin Xue and Lindsey Hayes for assistance with ELISAs. We also thank members of the Green lab, including Dr. Rachel Green and Dr. Boris Zinshteyn, for their expertise in RNA biology. The SMG1i compound was generously provided by the Cystic Fibrosis Foundation. This work was supported by T32GM007445 (for B.L.Z.) and funding from the Robert Packard Center for ALS Research and NIH-NINDS ( R01NS094239 to T.E.L. and J.D.R., R01NS107347 to S.S., K08NS104273 to L.R.H.), Target ALS (S.S.), and ALSA (S.S. and T.E.L.). Z.Z. and A.N.C. are recipients of the ALSA Milton Safenowitz Postdoctoral Fellowship. Funding Information: We thank the ALS patients and their families for essential contributions to this research and the Target ALS Human Postmortem Tissue Core for providing postmortem human tissue. We thank Xiaopei Tang and Weibo Zhou for expert assistance with iPSC differentiations and Lin Xue and Lindsey Hayes for assistance with ELISAs. We also thank members of the Green lab, including Dr. Rachel Green and Dr. Boris Zinshteyn, for their expertise in RNA biology. The SMG1i compound was generously provided by the Cystic Fibrosis Foundation. This work was supported by T32GM007445 (for B.L.Z.) and funding from the Robert Packard Center for ALS Research and NIH-NINDS (R01NS094239 to T.E.L. and J.D.R. R01NS107347 to S.S. K08NS104273 to L.R.H.), Target ALS (S.S.), and ALSA (S.S. and T.E.L.). Z.Z. and A.N.C. are recipients of the ALSA Milton Safenowitz Postdoctoral Fellowship. Conceived and designed the experiments, B.L.Z. Z.Z. K.M. T.E.L. S.S. and J.D.R.; performed the experiments, B.L.Z. Z.Z. K.M. A.N.C. W.C. and L.R.H.; analyzed the data, B.L.Z. Z.Z. and K.M.; contributed reagents and materials, B.L.Z. Z.Z. K.M. A.N.C. W.C. L.R.H. T.E.L. S.S. and J.D.R.; wrote the manuscript, B.L.Z. Z.Z. S.S. and J.D.R. with input from co-authors. The authors declare no competing interests. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = mar,
day = "30",
doi = "10.1016/j.celrep.2021.108925",
language = "English (US)",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}