Science Spotlight: Toxic proteins, not RNAs, the main driver of ALS/FTD phenotypes

A team led by Clotilde Lagier-Tourenne at the Broad Institute of MIT and Harvard and Franck Martin at the  University of Strasbourg published a Science paper that may finally tip a decade‑long debate in C9orf72‑linked ALS/FTD: is the main neurodegeneration driver from toxic RNA or toxic proteins?

In C9orf72‑related ALS/FTD, the GGGGCC hexanucleotide repeat mutation makes long repeated RNA sequences that can cause two potential problems: the repeat RNAs themselves form clumps (RNA foci) that might be toxic, or those same RNAs can be translated using repeat-associated non-AUG (RAN) translation into dipeptide repeat proteins (DPRs), which might be toxic...