Modulation of insulin signalling could be an effective therapeutic approach against hexanucleotide repeat expansion related to c9ALS/FTD neurodegenerative diseases.

Expanded repeat RNAs associated with human neurodegenerative diseases can become incorporated into transported granules in neurons, perturbing their function to cause neuritic branching defects.

Protein aggregates resulting from mutations in C9orf72 impair different aspects of cellular quality control in the cytosol and the nucleus, but mRNA-mediated effects contribute more strongly to toxicity.

Zfp106 functions as an RNA binding protein, binds directly to GGGGCC RNA repeats, is required in motor neurons to prevent ALS-like neurodegeneration in mice, and can suppress neurotoxicity in an established fly model of ALS.

Impaired nuclear import of the transcription factor TFEB/MITF is a major cause of autophagy and lysosome dysfunction in amyotrophic lateral sclerosis caused by mutations in the C9orf72 gene.

The crystal structure of Pur-alpha in complex with DNA reveals its molecular mechanisms of nucleic-acid binding and unwinding, allowing for a better understanding of its essential role in neurons.

Mutational analysis in cell-based models of C9ORF72 ALS/FTD identifies canonical translation initiation codons (AUG) on the antisense CCCCGG transcript as initiation sites for synthesis of neurotoxic dipeptide repeat proteins.

Poly-PR and poly-GR interact with importin β, disrupt importin-cargo loading, and inhibit nuclear import in permeabilized cells in a manner that can be rescued by RNA.

The C9orf72 expansion binds and sequesters the splicing factor hnRNP H leading to insoluble G-quadruplex aggregates that functionally reduce hnRNP H, thereby producing splicing defects.

C9ORF72 antisense repeat expanded RNAs activate PKR/eIF2α dependent integrated stress response and cause neuronal toxicity independent of DPR proteins.