Expanded Glutamine Repeat Enhances Complex Formation of Dentatorubral-Pallidoluysian Atrophy (DRPLA) Protein in Human Brains

Abstract

The genetic defect in dentatorubral-pallidoluysian atrophy (DRPLA) is expansion of the CAG repeat. The mutant gene is translated into the protein which carries the expanded glutamine repeat. Immunoblots of human brain tissues with and without reduction show that the DRPLA protein is a disulfide-bond complex and that more of this complex is formed in DRPLA brains than in control brains. This suggests that DRPLA protein undergoes greater complex formation in DRPLA brains and the expanded glutamine repeat may enhance complex formation of untruncated DRPLA protein in DRPLA brains. Immunohistochemical findings show that DRPLA protein is localized in the cytoplasm of the neuron, evidence that it undergoes rare disulfide bonding there.