Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology.
Here, we discuss the putative molecular mechanisms underlying FXTAS and notably recent reports that expanded CGG and GGC repeats may be pathogenic through RAN translation into toxic proteins.
RAN proteins have been reported in a growing number of diseases, including spinocerebellar ataxia type 8 (SCA8), myotonic dystrophy type 1 (DM1), Fragile-X tremor ataxia syndrome (FXTAS), and C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD).