Failure of the ubiquitin-proteasome system in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by degeneration of dopamine-containing neurons in the midbrain. In cases of familial PD, mutations that lead to failure of the ubiquitin-proteasome system (UPS) have been identified. These genetic abnormalities do not occur in sporadic PD, but we propose that impairment of the UPS could also contribute to neurodegeneration in this disorder, We discuss evidence that failure of the UPS is a common aetiopathogenic factor that underlies the development of familial and sporadic PD, an idea that might help to explain clinical and pathological differences and similarities in these disorders.