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

Uninterrupted CAG repeat length determines onset age in Huntington's disease, and therefore, base editing strategies to generate CAA interruption offer new therapeutic opportunities as they diminish the disease-causing mutation.

Alteration of the G-quadruplex structure formed by GGGGCC repeat RNA through the direct interaction with RNA-binding proteins can suppress pathogenic repeat-associated non-AUG translation, leading to therapeutic effects on neurodegeneration in C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia.

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

Somatic instability of the CAG repeat increases progressively with age and disease progression in Huntington disease mutation carriers, starting with low levels in fetal brain tissues.

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.

Genetic knockout of Hdac2 modifies molecular and cellular phenotypes in Huntington’s disease mice and has a prominent transcriptional regulatory role in adult medium spiny neurons.

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

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.

A novel sequencing-based method to characterize CNBP microsatellite expansions in DM2 patients demonstrates benefits for an improved dissection of DM2 genetic architecture, thus potentially ameliorating patient stratification and genetic counseling.