Emma L. Scotter

TL;DR: It is demonstrated that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos and proposed that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

TL;DR: In this paper, an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS) was performed and the results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein.

TL;DR: It is demonstrated how diverse environmental stressors linked to stress granule formation, as well as mutations in genes encoding RNA processing proteins and protein degradation adaptors, initiate ALS pathogenesis via TDP-43.

TL;DR: It is found that soluble TDP-43 is degraded primarily by the UPS, whereas the clearance of aggregated T DP-43 requires autophagy, andTherapies for clearing excess TTP-43 should target a combination of these pathways.

TL;DR: It is demonstrated that C-terminal ALS mutations disrupt the nuclear localizing signal (NLS) of FUS resulting in cytoplasmic accumulation in transfected cells and patient fibroblasts, and this findings support a two-hit hypothesis, whereby cytopLasmic mislocalization of F US protein, followed by cellular stress, contributes to the formation of cytopal aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.