Abstract
Neurodegeneration Stress granules are membraneless organelles composed of RNAs and proteins that can accumulate in the presence of potentially pathogenic proteins. These include proteins linked to neurodegenerative disorders such as C9-ALS/FTD (amyotrophic lateral sclerosis and frontotemporal dementia linked to C9ORF72). The pathomechanisms of these same disorders can involve disruption of nucleocytoplasmic transport. Zhang et al. found that a variety of components of the nuclear import machinery were sequestered in stress granules, which reduced nucleocytoplasmic transport. Inhibiting stress granule assembly suppressed these transport defects in cells, and it also interfered with the neurodegeneration process in patient-derived iPS (induced pluripotent stem cell–derived) motor neurons and in a fly C9-ALS disease model system. Cell 173 , 958 (2018).
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