Mechanisms of neurodegeneration and neuroprotection in Parkinson's and Huntington's diseases.
Dr. Greenamyre’s lab is interested in mechanisms that cause nerve cell death in disorders such as Parkinson's, Huntington's, and Alzheimer's diseases. The work focuses on mitochondrial impairment, oxidative damage, protein aggregation, calcium homeostasis, and excitotoxicity. The general strategy is to define mechanisms that cause nerve cell death, and then use them as potential "targets" for therapeutic intervention. The lab employs in vivo models of neurodegeneration and in vitro culture of cells and brain slices to study mechanisms of degeneration with a variety of biochemical, anatomical, and physiological techniques. A novel model of Parkinson's disease has been developed and is being used to screen potential neuroprotective strategies (Nature Neuroscience 3:1301-1306, 2000). Peripheral cells from patients are also used for physiological studies (Nature Neuroscience 5:731-736, 2002). In vitro assays have been developed to screen for environmental toxicants that impair mitochondrial function. Additional screens have been devised for neuroprotectants.
Pallanck, L., Greenamyre, J.T. Neurodegenerative disease: pink, parkin and the brain. Nature. 441(7097): 1058, 2006.
Berman, S.B., Greenamyre, J.T. Update on Huntington's disease. Curr Neurol Neurosci Rep. 6(4): 281-6, 2006.
Richardson, J.R., Caudle, W.M., Guillot, T.S., Watson, J.L., Nakamaru-Ogiso, E., Seo, B.B., Sherer, T.B., Greenamyre, J.T., Yagi, T., Matsuno-Yagi, A. and Miller, G.W. Obligatory role for complex I inhibition in the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Toxicol Sci. 95(1): 196-204,2007. Epub 2006 Oct 12.
Sherer, T.B., Richardson, J.R., Testa, C.M., Seo, B.B., Panov, A.V., Yagi, T., Matsuno-Yagi, A., Miller, G.W. and Greenamyre, J.T. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Neurochem. 100(6):1469-79, 2007. Epub 2007 Jan 4.
Greenamyre, J.T. Huntington's disease--making connections. N Engl J Med. 356(5): 518-20, 2007.