The pathogenic mechanisms underlying Parkinson's disease (PD) remain enigmatic. In an effort to identify early molecular events associated with PD, we profiled genomic and proteomic changes in the MPTP mouse model of PD. cDNA and antibody microarray analysis revealed time-dependent (1h-48h) changes in striatal gene expression following dopaminergic neurotoxicity and associated reactive gliosis. A medley of genes exhibiting altered expression is tabulated. Other genes expressed included cytokines & chemokines, growth factors, transcription factors, protein kinases and genes related to stress, cell cycle and apoptosis. Further, by proteomic profiling using ProteinChip-SELDI-TOF we identified smaller peptides & proteins associated with MPTP-neurotoxicity. These included neuropeptides (substance P, neurokinin A, brain natriuretic peptide), neuronal protein 15.6, PEA-15, MRF-l, cytokines & chemokines (IL-9, IL-17, MCP-l, MCP-5, MIP-2, MIP-3), growth factors (BMP, CT-l, LIF), transcription factors (ATF-3, BTF-3, CREB-bp, IEF-3, NTF-2) and stress proteins (MT-IC, MT-1H, MT-3). These findings helped identify early effectors/mediators and have provided a foundation for (1) further characterization of candidate genes involved in the neurodegenerative process and (2) identifying potential targets for therapeutic intervention.
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah