NIH R01 · 2025
Expansion of a hexanucleotide GGGGCC repeat within the first intron of the C9orf72 gene is the primary monogenic cause for both Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Despite its intronic location, expanded GGGGCC repeat is retained in the mature mRNA, supporting a non-canonical translation initiation mechanism known as repeat- associated non-AUG (RAN) translation. RAN translation of C9orf72 mRNA generates toxic dipeptide repeat (DPR) proteins. These DPR proteins aggregate in the brains of affected individuals and have been shown to induce neurodegeneration in model systems. Despite the medical and biological importance of RAN translation, a fundamental…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.