Region-Specific Protein Abundance Changes in the Brain of MPTP-Induced Parkinson's Disease Mouse Model

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Title Region-Specific Protein Abundance Changes in the Brain of MPTP-Induced Parkinson's Disease Mouse Model
Author Zhang, Xu; Zhou, Jian-Ying; Chin, Mark H.; Schepmoes, Athena A.; Petyuk, Vladislav A.; Weitz, Karl K.; Petritis, Brianne O.; Monroe, Matthew E.; II, David G. Camp; Wood, Stephen Andrew; Melega, William P.; Bigelow, Diana J.; Smith, Desmond J.; Qian, Wei-Jun; Smith, Richard D.
Journal Name Journal of Proteome Research
Year Published 2010
Place of publication United States
Publisher American Chemical Society
Abstract Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/ MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify potential nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 nonredundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with substantial MPTP-induced abundance changes across different brain regions. A total of 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. Ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF- pathway, exhibited altered abundance in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1021/pr901024z
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 9
Issue Number 3
Page from 1496
Page to 1509
ISSN 1535-3893
Date Accessioned 2010-11-05
Date Available 2011-03-07T08:51:52Z
Language en_AU
Research Centre Eskitis Institute for Drug Discovery
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biochemistry and Cell Biology
URI http://hdl.handle.net/10072/36821
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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