Boeynaems, S., Bogaert, E., Michiels, E., Gijselinck, I., Sieben, A., Jovičić, A., De Baets, G., Scheveneels, W., Steyaert, J., Cuijt, I., Verstrepen, K.J., Callaerts, P., Rousseau, F., Schymkowitz, J., Cruts, M., Van Broeckhoven, C., Van Damme, P., Gitler, A.D., Robberecht, W., Van Den Bosch, L. (2016). Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD.  Sci. Rep. 6(): 20877.

FBrf0230967

Research paper

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.

PMC4751451 (PMC) (EuropePMC)