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Proteomic studies with alpha‐synuclein knockout mice
Author(s) -
Lakos Zsuzsa,
Fink Anthony L.
Publication year - 2006
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.20.4.a65-c
Subject(s) - substantia nigra , alpha synuclein , heat shock protein , microbiology and biotechnology , neurofilament , striatum , biology , knockout mouse , chemistry , biochemistry , dopaminergic , parkinson's disease , neuroscience , dopamine , medicine , gene , immunology , disease , immunohistochemistry
Parkinson’s disease (PD) is a chronic, progressive disorder of the central nervous system caused by the loss of dopaminergic neurons in the substantia nigra. To date there is no cure for Parkinson’s disease, and there are no biomarkers that could help diagnose or predict the disease. The aggregation of α‐synuclein, a presynaptic protein of unknown function, is regarded as a critical step in the development of Parkinson’s disease. In order to explore the biological role of α‐synuclein we carried out protein profiling studies with α‐synuclein gene knockout mice investigating different brain regions: striatum, front cortex, and ventromedial region. Proteins were separated and analyzed using 2D DIGE (differential‐in‐gel‐electrophoresis) methods followed by identification using MALDI‐TOF mass spectrometry and peptide mass fingerprinting. Over > 1800 brain proteins were separated. Analysis of samples from knockout mice showed significant changes (>150 protein changed by at least 20%). Approximately 80 of these proteins have been identified. Our results show significant changes in the level of heat shock proteins (Hsp 74, Hsp 70, protein 8, Hsp A); neurofilament proteins (alpha‐internexin 66 kDa filament protein, neurofilament 3), peroxiredoxin proteins (2 and 6), mitochondrial proteins (ATP synthase, mitochondrial F1 complex), phosphatidylethanolamine binding protein and platelet activating factor acetylhydrolase. The results indicate significant effects of the absence of α‐synuclein not only, as expected, in the striatum, but also other areas such as the frontal cortex.