Miranda L. Tradewell

TL;DR: Together these approaches showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.

TL;DR: It is proposed that arginine methylation by PRMT1 participates in the nuclear-cytoplasmic shuttling of FUS, particularly of ALS6-associated mutants, and thus contributes to the toxic gain of function conferred by these disease-causing mutations.

TL;DR: That geldanamycin prevented inclusions and mitochondrial rounding, but not Ca(2+) dysregulation or loss of Δψ indicates that chaperone-based therapies to prevent protein aggregation may require co-therapy to address these other underlying mechanisms of toxicity.

TL;DR: There are NFL mutant-specific differences in the ability of individual HSPs to prevent neurofilament abnormalities, reduction in axonal caliber, and disruption of mitochondrial morphology in motor neurons, suggesting that HSP inducers have therapeutic potential for CMT2E but that their efficacy would depend on the profile of HSPS induced and the type of NEFL mutation.

TL;DR: Evidence is provided for loss of PRMT1 function as a consequence of cytoplasmic accumulation of FUS in the pathogenesis of ALS, including changes in the histone code regulating gene transcription.