Emory Parkinson’s Disease Collaborative Environmental Research Center
Gary Miller, Ph.D.
The Emory Parkinson’s Disease Collaborative Environmental Research Center works to understand how environmental contaminants such as pesticides contribute to Parkinson’s disease. Researchers at the Center examine how environmental contaminants disrupt important cellular functions in the substantia nigra, an area of the brain involved in movement. They also study how neurons respond to environmental insults and are identifying measurable biological indicators, known as biomarkers, associated with environmental exposures and with Parkinson’s disease.
The center has identified key mechanisms that are likely involved in the disease and have developed innovative tools to advance research in this area. This research is revealing information that can help prevent, diagnose, and treat Parkinson’s disease.
Project leader: Gary Miller, Ph.D.
Parkinson’s disease is associated with the loss of neurons that produce the neurotransmitter dopamine in the substantia nigra area of the brain. Researchers involved in this project have shown that many environmental chemicals inhibit the vesicular monoamine transporter (VMAT). This protein plays an important role in the transport of neurotransmitters such as dopamine, and it appears to affect the vulnerability of dopamine-producing neurons. The researchers developed new tools, including a mouse line, a fluorescence assay, and a mathematical model, to study VMAT’s role in Parkinson's disease.
Project leader: Zixu Mao, M.D., Ph.D.
This project studies how environmental contaminants can disrupt the function of mitochondria in a way that leads to the loss of dopamine-secreting neurons. Mitochondria generate the energy that cells need to function. The researchers investigate the transcription factor myocyte enhancer factor 2 (MEF2), which they have shown is present in mitochondria. The researchers want to understand MEF2’s involvement in the toxicity of environmental contaminants associated with Parkinson’s disease. Their work is showing that MEF2 is a promising therapeutic target.
Project leader: Dean Jones, Ph.D.
In this project, researchers study environmental contributors to Parkinson's disease using metabolomics. Metabolomics involves analyzing the byproducts of our body’s metabolism, known as metabolites, to gain information about chemical exposures and disease. The researchers perform high-throughput analysis on biological samples to identify unique metabolic signatures tied to pesticide exposures and Parkinson’s disease development. These signatures could reveal new targets for therapy and new ways to detect risk for Parkinson’s disease. The investigators have combined novel data analysis techniques with the latest analytical instruments to progressively increase the number of detectable metabolites to more than 44,000. Preliminary results show that metabolites can be identified that discriminate high vs. low exposures and rapid vs. slow progression in Parkinson’s disease patients.
- Bernstein AI, Stout KA, Miller GW. A fluorescent-based assay for live cell, spatially resolved assessment of vesicular monoamine transporter 2-mediated neurotransmitter transport. 2012. J Neurosci Methods. 209(2):357-366.[Abstract]
- Caudle WM, Guillot TS, Lazo CR, Miller GW. 2012. Industrial toxicants and Parkinson's disease. Neurotoxicology 33(2):178-188. (review)[Abstract]
- Roede JR, Park Y, Li S, Strobel FH, Jones DP. 2012. Detailed mitochondrial phenotyping by high resolution metabolomics. PLoS ONE 7(3): e33020.[Abstract]
- Park YP, Lee K, Soltow QA, Strobel FH, Brigham KL, Parker RE, Wilson ME, Sutliff RL, Mansfield KG, Wachtman LM, Ziegler TR, Jones DP. 2012. High-performance metabolic profiling of plasma from seven mammalian species for simultaneous environmental chemical surveillance and bioeffect monitoring. Toxicology 295(1-3):47-55.[Abstract]
- She H, Yang Q, Mao Z. 2012. Neurotoxin-induced selective ubiquitination and regulation of MEF2A isoform in neuronal stress response. J Neurochem; doi:10.1111/j.1471-4159.2012.07860.x. [Online 3 August 2012].[Abstract]
- Roede JR, Hansen JM, Go YM, Jones DP. 2011. Maneb and paraquat-mediated neurotoxicity: involvement of peroxiredoxin/thioredoxin system. Toxicol Sci. 121 (2): 368-375.[Abstract]
- Hatcher-Martin JM, Gearing M, Steenland K, Levey AI, Miller GW, Pennell KD. In press. Association between polychlorinated biphenyls and Parkinson’s disease neuropathology. Neurotoxicology.
- Soltow QA, Strobel FH, Mansfield KG, Wachtman L, Park Y, Jones DP. 2011. High-performance metabolic profiling with dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) for study of the exposome, Metabolomics; DOI: 10.1007/s11306-011-0332-1 [Online 8 July 2011].[Abstract]
- She H, Yang Q, Shepherd K, Smith Y, Miller G, Testa C, Mao Z. 2011. Direct regulation of complex I by mitochondrial MEF2D is disrupted in a mouse model of Parkinson disease and in human patients. J Clin Invest 121(3):930-940.[Abstract]
- Vrailas-Mortimer A, del Rivero T, Mukherjee S, Nag S, Gaitanidis A, Kadas D, Consoulas C, Duttaroy A, Sanyal S. 2011. A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila. Dev Cell 21(4):783-795.[Abstract]
- Taylor TN, Caudle WM, Shepherd KR, Noorian A, Jackson CR, Iuvone PM, Weinshenker D, Greene JG, Miller GW. 2009. Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity. J Neurosci 29(25):8103-8113.[Abstract]
- Orr AG, Orr AL, Li XJ, Gross RE, Traynelis SF. 2009. Adenosine A(2A) receptor mediates microglial process retraction. Nat Neurosci 12(7):872-878.[Abstract]
- Wang X, She H, Mao Z. 2009. Phosphorylation of neuronal survival factor MEF2D by glycogen synthase kinase 3beta in neuronal apoptosis. J Biol Chem. 284(47):32619-32626.[Abstract]