Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS

Ana Jovičič, Jerome Mertens, Steven Boeynaems, Elke Bogaert, Noori Chai, Shizuka B. Yamada, Joseph W. Paul, Shuying Sun, Joseph R. Herdy, Gregor Bieri, Nicholas J. Kramer, Fred H. Gage, Ludo Van Den Bosch, Wim Robberecht, Aaron D. Gitler

Research output: Contribution to journalArticlepeer-review

Abstract

C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) produced by unconventional translation of the C9orf72 repeat expansions cause neurodegeneration in cell culture and in animal models. We performed two unbiased screens in Saccharomyces cerevisiae and identified potent modifiers of DPR toxicity, including karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets.

Original languageEnglish (US)
Pages (from-to)1226-1229
Number of pages4
JournalNature neuroscience
Volume18
Issue number9
DOIs
StatePublished - Aug 26 2015

ASJC Scopus subject areas

  • Neuroscience(all)

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