Congo red, doxycycline, and HSP70 overexpression reduce aggregate formation and cell death in cell models of oculopharyngeal muscular dystrophy

Abstract
The second type of codon reiteration mutation results in autosomal dominant oculopharyngeal muscular dystrophy (OPMD).4 OPMD is caused by the abnormal expansion of a (GCG)n trinucleotide repeat in the coding region of the polyadenine binding protein 2 gene (PABP2): a (GCG)6 repeat is expanded to (GCG)8–13 in most patients. In some rare cases, insertion mutations such as (GCG)6GCA(GCG)2, (GCG)6GCA(GCG)3 and (GCG)6(GCA)3(GCG)2 are seen.5, 6 In PABP2, (GCG)6 codes for the first six alanines in a homopolymeric stretch of 10 alanines. Thus, disease is associated with expansions of 12 or more uninterrupted alanines in this nuclear protein. OPMD is characterised by aggregates in muscle cell nuclei comprising mutant PABP2 as a major component.4, 7– 9