The molecular mechanisms of neurodegeneration due to a repeat expansion in C9orf72, the most common cause of frontotemporal dementia and amyotrophic lateral sclerosis, are unknown. Three reports now link compromised nucleocytoplasmic transport to disease pathogenesis. Whether RNA structures or dipeptide repeat proteins are most toxic in humans remains open to question.
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Acknowledgements
M.v.B. is supported by the Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Clinical Research Fellowship (U54 NS092091). R.R. is funded by NIH grants R01 NS080882, R01 NS076471, P50 AG016574, P01 NS084974, the Consortium for Frontotemporal Dementia and the ALS Therapy Alliance.
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R.R. holds a patent on methods to screen for the hexanucleotide repeat expansion in the C9orf72 gene. M.v.B. declares no competing interests.
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van Blitterswijk, M., Rademakers, R. C9orf72 repeats compromise nucleocytoplasmic transport. Nat Rev Neurol 11, 670–672 (2015). https://doi.org/10.1038/nrneurol.2015.219
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DOI: https://doi.org/10.1038/nrneurol.2015.219
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