Dentatorubral-pallidoluysian atrophy (DRPLA) is caused by expansion of a 
glutamine repeat in DRPLA protein. DRPLA protein undergoes greater complex 
formation in DRPLA brain tissue, and expanded glutamine repeat enhances complex 
formation of DRPLA protein. Immunoblots with and without reduction show that the 
DRPLA protein complex is ubiquitinated only in DRPLA brain tissue. Moreover, 
immunoblots of regional DRPLA brain tissues reveal that pathological 
ubiquitination of DRPLA protein complex is found selectively in affected 
lesions. Double-labeling immunohistochemical studies with antibodies against 
DRPLA protein and ubiquitin demonstrate that the DRPLA protein is co-localized 
with ubiquitin in DRPLA neurons and show characteristic neuronal cytoplasmic 
inclusions with ubiquitinated DRPLA protein complex in the center. Our findings 
suggest that DRPLA protein undergoes abnormal complex formation with expanded 
glutamine repeat, and then the complex is pathologically ubiquitinated in DRPLA 
brain tissue. Pathological ubiquitination of abnormal DRPLA protein complex 
plays a role in DRPLA pathology.