EXPANDED GLUTAMINE REPEAT ENHANCES COMPLEX-FORMATION OF DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) PROTEIN IN HUMAN BRAINS

The genetic defect in dentatorubral-pallidoluysian atrophy (DRPLA) is expansion of the CAG repeat. The mutant gene is translated into the pr otein which carries the expanded glutamine repeat. Immunoblots of huma n brain tissues with and without reduction show that the DRPLA protein is a disulfide-bond complex and that more of this complex is formed i n DRPLA brains than in control brains. This suggests that DRPLA protei n undergoes greater complex formation in DRPLA brains and the expanded glutamine repeat may enhance complex formation of untruncated DRPLA p rotein in DRPLA brains. Immunohistochemical findings show that DRPLA p rotein is localized in the cytoplasm of the neuron, evidence that it u ndergoes rare disulfide bonding there. (C) 1998 Academic Press.