Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS

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 tw...

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Autores principales: Jovičić, Ana, Mertens, Jerome, Boeynaems, Steven, Bogaert, Elke, Chai, Noori, Yamada, Shizuka B., Paul, Joseph W., Sun, Shuying, Herdy, Joseph R., Bieri, Gregor, Kramer, Nicholas J., Gage, Fred H., Den Bosch, Ludo Van, Robberecht, Wim, Gitler, Aaron D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552077/
https://www.ncbi.nlm.nih.gov/pubmed/26308983
http://dx.doi.org/10.1038/nn.4085
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author Jovičić, Ana
Mertens, Jerome
Boeynaems, Steven
Bogaert, Elke
Chai, Noori
Yamada, Shizuka B.
Paul, Joseph W.
Sun, Shuying
Herdy, Joseph R.
Bieri, Gregor
Kramer, Nicholas J.
Gage, Fred H.
Den Bosch, Ludo Van
Robberecht, Wim
Gitler, Aaron D.
author_facet Jovičić, Ana
Mertens, Jerome
Boeynaems, Steven
Bogaert, Elke
Chai, Noori
Yamada, Shizuka B.
Paul, Joseph W.
Sun, Shuying
Herdy, Joseph R.
Bieri, Gregor
Kramer, Nicholas J.
Gage, Fred H.
Den Bosch, Ludo Van
Robberecht, Wim
Gitler, Aaron D.
author_sort Jovičić, Ana
collection PubMed
description 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, uncovering karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets.
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spelling pubmed-45520772016-03-01 Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS Jovičić, Ana Mertens, Jerome Boeynaems, Steven Bogaert, Elke Chai, Noori Yamada, Shizuka B. Paul, Joseph W. Sun, Shuying Herdy, Joseph R. Bieri, Gregor Kramer, Nicholas J. Gage, Fred H. Den Bosch, Ludo Van Robberecht, Wim Gitler, Aaron D. Nat Neurosci Article 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, uncovering karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets. 2015-09 /pmc/articles/PMC4552077/ /pubmed/26308983 http://dx.doi.org/10.1038/nn.4085 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jovičić, Ana
Mertens, Jerome
Boeynaems, Steven
Bogaert, Elke
Chai, Noori
Yamada, Shizuka B.
Paul, Joseph W.
Sun, Shuying
Herdy, Joseph R.
Bieri, Gregor
Kramer, Nicholas J.
Gage, Fred H.
Den Bosch, Ludo Van
Robberecht, Wim
Gitler, Aaron D.
Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title_full Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title_fullStr Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title_full_unstemmed Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title_short Modifiers of C9orf72 DPR toxicity implicate nucleocytoplasmic transport impairments in c9FTD/ALS
title_sort modifiers of c9orf72 dpr toxicity implicate nucleocytoplasmic transport impairments in c9ftd/als
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552077/
https://www.ncbi.nlm.nih.gov/pubmed/26308983
http://dx.doi.org/10.1038/nn.4085
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