Aberrant phosphorylation of dentatorubral-pallidoluysian atrophy (DRPLA) protein complex in brain tissue.

Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by DRPLA protein which carries expansion of a glutamine repeat. Abnormal high-molecular-mass complex formation by DRPLA protein and its pathological ubiquitination comprise the disease processes in the brains of patients with DRPLA. In this study, DRPLA protein complex was isolated and shown to have pathologically stronger bond formation with DRPLA proteins in DRPLA brain tissue compared with control brain tissue. Immunochemical methods and an enzymic dephosphorylation technique were used to demonstrate that DRPLA protein complex is aberrantly phosphorylated in DRPLA brain tissue. Immunohistochemical studies show that both the ubiquitinated cytoplasmic inclusions and the nuclear membrane are aberrantly phosphorylated in DRPLA-affected neurons. This finding suggests that the nuclear membrane is another pathological focus of DRPLA neurodegeneration.