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

Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by DRPLA protein whi ch carries expansion of a glutamine repeat. Abnormal high-molecular-mass co mplex formation by DRPLA protein and its pathological ubiquitination compri se the disease processes in the brains of patients with DRPLA. In this stud y, DRPLA protein complex was isolated and shown to have pathologically stro nger bond formation with DRPLA proteins in DRPLA brain tissue compared with control brain tissue. Immunochemical methods and an enzymic dephosphorylat ion technique were used to demonstrate that DRPLA protein complex is aberra ntly phosphorylated in DRPLA brain tissue. Immunohistochemical studies show that both the ubiquitinated cytoplasmic inclusions and the nuclear membran e are aberrantly phosphorylated in DRPLA-affected neurons. This finding sug gests that the nuclear membrane is another pathological focus of DRPLA neur odegeneration.