Are RNA Foci Pathogenic or Protective?
Neurodegenerative diseases, such as Alzheimer disease and those caused by polyglutamine expansions, result in protein aggregates or plaques and tangles that accumulate in affected tissues and have led investigators to debate their role in disease pathogenesis (Hsiao et al. 1995; Klement et al. 1998). Similar discussions in the DM field revolve around the role of RNA foci in disease pathogenesis. CUG-BP, the first RNA-binding protein with a demonstrated pathogenic effect, has been shown to bind to single-stranded CUG repeats. In contrast with the muscleblind family of proteins, CUG-BP does not colocalize with the nuclear RNA foci in DM1 and DM2. Although it appeared possible that both groups of proteins play a role in the pathogenic effects of DM, colocalization of a protein to the ribonuclear inclusions did not appear to be necessary to cause a pathogenic effect.
