The manifestation of Lewy bodies (LB) in the brain is a hallmark of Parkinson's 
disease. Here, we present a comprehensive analysis of protein elements in Lewy 
bodies by comparative mass spectrometry. Cortical LB inclusions were enriched by 
sucrose gradient centrifugation from postmortem brains, and a negative control 
sample was prepared from specimen without LB pathology. Whereas approximately 
550 proteins were identified in the LB-enriched sample by mass spectrometry, 
quantitative comparison with the control sample revealed that approximately 40 
proteins were co-enriched with alpha-synuclein, the major component in Lewy 
bodies. As expected, the list of proteins included previously reported 
constituents, such as those involved in protein folding, membrane trafficking 
and oxidative stress. More interestingly, we discovered in the LB-enriched 
sample several kinases (MAPKK1/MEK1, protein kinase C, and doublecortin-like 
kinase), a novel deubiquitinating enzyme (otubain 1), and numerous ubiquitin 
ligases (KPC and SCF). The proteomic studies provide enzyme candidates to 
investigate the regulation of alpha-synuclein and/or other LB proteins, which 
may contribute to the formation of Lewy bodies and the toxicity of 
alpha-synuclein in the related neurodegenerative disorders.