Brain proteasomal function in sporadic Parkinson's disease and related disorders

Because genetic defects relating to the ubiquitin-proteasome system were reported in familial parkinsonism, we evaluated proteasomal function in autopsied brains with sporadic Parkinson's disease. We found that proteasome peptidase activities in a fraction specific to the proteasome were preserved in five brain areas (including the striatum) of Parkinson's disease where neuronal loss is not observed. Striatal protein levels of two proteasome subunits were normal in Parkinson's disease but reduced mildly in disease controls (multiple system atrophy). Our brain data suggest that a systemic, global disturbance in the catalytic activity and degradation ability of the proteasome itself is unlikely to explain the cause of Parkinson's disease.