My lab is primarily interested in understanding the molecular and cellular basis of mutant copper zinc superoxide dismutase (SOD1) toxicity in causing one form of familial amyotrophic lateral sclerosis. Mutations in this protein cause disease by a toxic gain function in which protein aggregation is likely an important component. My lab uses a combination of techniques from molecular neurobiology, cell biology, transgenic approaches, and proteinomics to understand the basis of disease in an ALS animal model.
One focus in the lab is to understand the basis for SOD1 protein aggregation and clearance of SOD1 positive aggregates in neuronal cells. We have recently generated novel mutations in this protein to understand what domains within the molecule are critical in its aggregation potential. Future studies will involve understanding the biological ramifications of this in vivo using transgenic animals. We are also interested in how proteasomes degrade and clear SOD1 protein complexes, both in vitro and in vivo.
Another primary focus of the lab is to understand mechanisms which regulate the sub-cellular localization of SOD1 and assess what effect differential sub-cellular localization has in disease pathogenesis. We have recently found that a chaperone protein increases SOD1 expression within mitochondria and dramatically changes the motor phenotype of the transgenic mice. We plan to extend these findings by understanding how SOD1 localization within mitochondrial leads to mitochondria destruction and the disease state.
RECENT PUBLICATIONS
M Son, K Puttaparthi, H Kawamata, B Rajendran, PJ Boyer, G Manfredi and JL Elliott, ""Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology"" PNAS, 104::6072-6077, April 2007
K Puttaparthi and JL Elliott,, ""Assessing the role of immuno-proteasomes in a mouse model of familial ALS"" Experimental Neurology, 206::53-58, July 2007
Son, M., Leary, S.C., Romain, N., Pierrel, F., Winge, D.R., Haller, R.G., and Elliott, J.L.,, ""Isolated Cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein"" The Journal of Biological Chemistry, 283::12267-12275,, May 2008
Proescher JB, Son M, Elliott JL, Culotta VC,, ""Biological effects of CCS in the absence of SOD1 enzyme activation: implications for disease in a mouse model of ALS"" Human Molecular Genetics, 17::1728-1737., 2008
Son M, Fu Q, Puttaparthi K, Matthews CM and Elliott JL., ""Redox susceptibility of SOD1 mutants is associated with the differential resonse to CCS over-expression in vivo"" Neurobiology of Disease, In press 2009
K Puttaparthis and JL Elliott, ""Assessing the role of immuno-prpteasomes in a mouse model of familial ALS"" Experimental Neurology, 206::53-58, July 2007
SIGNIFICANT PUBLICATIONS
K Puttparthi, WL Gitomer U Krishnan, M Son, B Rajendran, and JL Elliott, ""Disease Progression in Transgenic model of familial amyotrophic latera sclerosis is dependent on both Neuronal and non-neuronal zinc binding proteins."o" Journal of Neuroscience,, 22::8790-8796, October 2002
Elliott JL,, ""Upregulation of cytokine expression in a transgenic model of familial amyotrophic lateral sclerosis"" Molecular Brain Research, 95::172-178, 2001
Honig LS, Chambliss D, Bigio E, Carroll S, Elliott JL, ""Glutamate transorter EAAT-2 splice variants occur not only in ALS, but also in AD and controls"" Neurology, 55::1082-1088, 2000
Gong YH, Parsadanian A, Andreeva A, Snider WD, Elliott,JL,, ""Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoreuron degeneration"" Journal of Neuroscience,, 20(2)::660-665, 2000
Reaume AG, Elliott JL, Hoffman EK, et al,, ""Motor Neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury"" Nature Genetics, 13::43-47, 1996
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