The Evolution of Phase-Separated TDP-43 in Stress

In this issue of Neuron, Gasset-Rosa et al. (2019) and Mann et al. (2019) demonstrate that cytoplasmic inclusions containing aggregated phosphorylated TDP-43 can evolve through three pathways: direct aggregation or phase-separated intermediates involving ejection from stress granules or seeding with exogenous fibrils. Interestingly, seeding with exogenous fibrils also induces cytoplasmic aggregates of nuclear pore proteins.