This work describes an optogenetic method to induce TDP-43 proteinopathy (optoTDP43), a pathological hallmark of ALS/FTD, in live cells. We use this approach and show that RNA binding to antagonizes the formation of inclusions and this is independent of RNA containing stress granules. Importantly, we were able to inhibit the formation of optoTDP43 inclusions and associated cytotoxicity with oligonucleotides that target TDP-43.
Nature Reviews Neuroscience, 2016
This is a comprehensive review of the pathobiology of C9orf72 ALS/FTD and outlines potential avenues for therapeutic intervention.
This is the first study to identify and characterize the mechanism underlying nucleocytoplasmic transport deficits and nuclear pore pathobiology in C9orf72 ALS/FTD patient iPSC motor neurons and Drosophila models.
This work describes the G-quadruplex DNA/RNA structure of the C9orf72 ALS/FTD repeat expansion and the contribution of this structure on C9ORF72 transcription and nucleolar function.
This study employs induced pluripotent stem cell (iPSC) motor neurons from C9orf72 ALS/FTD patients and identifies gain of function mechanism of neurotoxicity that are rescued with treatment of antisense oligonucleotide therapeutics.