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Proteomics Identification of Novel Proteins Involved in Lewy Body Progression
Author(s) -
Zhang Jing
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a28-c
Subject(s) - proteomics , lewy body , pathogenesis , biology , neuroscience , proteome , microbiology and biotechnology , blot , pathology , disease , dementia , medicine , bioinformatics , biochemistry , immunology , gene
One of the key pathological features of Parkinson's disease (PD) and PD dementia is formation of Lewy bodies (LBs) in various brain regions. Braak and colleagues have conducted several elegant studies using PD patients at various stages as well as nonsymptomatic cases, demonstrating that pathological changes in PD follow an ascending course as the disease progresses with little interindividual variation. However, very little is known as to the pathogenesis that underlies LB progression, although recent studies appear to suggest that synaptic dysfunction could be one of the important cellular processes involved. To identify novel synaptic proteins involved in LB diseases, we prepared synaptosomal fractions from the frontal cortex of PD patients at different stages, including predominant brainstem LB, predominant limbic LB, and diffuse LB, along with age‐matched controls. Synaptosomic proteins were analyzed with a robust quantitative proteomic technique called Isobaric Tags for Relative and Absolute Quantification (iTRAQ). Ongoing analysis has identified 1295 proteins thus far; of those, 64 proteins were found to be progressively increased as the disease advances, including calcium/calmodulin‐dependent protein kinase II and heat shock 70 kDa protein 6. There were also 17 proteins, e.g. CNPII and myelin associated glycoprotein, which progressively decreased as the disease advances. We are currently verifying these results using Western blotting as well as confocal microscopy. The biology of a few candidate proteins are also being pursued using various cellular models of PD.