Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD

Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modif...

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Detalles Bibliográficos
Autores principales: Boeynaems, Steven, Bogaert, Elke, Michiels, Emiel, Gijselinck, Ilse, Sieben, Anne, Jovičić, Ana, De Baets, Greet, Scheveneels, Wendy, Steyaert, Jolien, Cuijt, Ivy, Verstrepen, Kevin J., Callaerts, Patrick, Rousseau, Frederic, Schymkowitz, Joost, Cruts, Marc, Van Broeckhoven, Christine, Van Damme, Philip, Gitler, Aaron D., Robberecht, Wim, Van Den Bosch, Ludo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751451/
https://www.ncbi.nlm.nih.gov/pubmed/26869068
http://dx.doi.org/10.1038/srep20877
Descripción
Sumario:Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD.

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