Center for Neurodegenerative and Neuroimmunologic Diseases

Department of Neurology

The Center’s mission is to promote translational research and to foster the application of a wide range of current biological methods for the objective of elucidating the pathogenesis of and developing novel therapies for certain chronic incurable neurological conditions, with a particular emphasis on Parkinson’s disease (PD) and Multiple Sclerosis (MS). Specific goals include the conduct of basic research in the molecular pathogenesis of PD with a focus on the role of genetic mutations in protein aggregation and dopaminergic neuronal cell death; identification of targets for therapeutic interventions in PD and test those targets in transgenic animal models; the conduct of studies on the basic immune mechanisms of therapies for Multiple Sclerosis and the identification of biomarkers of treatment response; and developing strategies to deliver therapeutic genes into the brain using bone marrow cells as vehicles.

The educational goals of the Center are to provide an environment for training post-doctoral fellows and physician scientists in neurodegenerative and neuroimmunological diseases, and to provide elective time for Neurology residents or trainees from other departments who wish to explore research opportunities in neurologic diseases.

Selected recent publications from the Center:

1. Junn, E., Ronchetti, R.D., Quezado, M.M., Kim, S.-Y., Mouradian, M.M.: Tissue transglutaminase-induced aggregation of -synuclein: Implications for Lewy body formation in Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA, 100(4):2047-2052, 2003.
2. Lee, S.S., Kim, Y.M., Junn, E., Lee, G., Park, K.-H., Tanaka, M., Ronchetti, R.D., Quezado, M., Mouradian, M.M.: Cell cycle aberrations by -synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. Neurobiol. Aging, 24(5):687-696, 2003.
3. Tanaka, M., Kim, Y.M., Lee, G., Junn, E., Iwatsubo, T., Mouradian, M.M.: Aggresomes formed by -synuclein and synphilin-1 are cytoprotective. J. Biol. Chem., 279(6):4625-4631, 2004.
4. Lee, G., Tanaka, M., Park, K., Lee, S.S., Kim, Y.M., Junn, E., Lee, S.H., Mouradian, M.M.: Casein kinase II mediated phosphorylation regulates -synuclein / synphilin-1 interaction and inclusion body formation. J. Biol. Chem., 279(8):6834-6839, 2004.
5. Junn, E., Taniguchi. H., Jeong, B.S., Zhao, X., Ichijo, H., Mouradian, M.M.: Interaction of DJ-1 with Daxx inhibits ASK1 activity and cell death. Proc. Natl. Acad. Sci. USA, 102(27): 9691-9696, 2005.
6. Chen, M. and Dhib-Jalbut, S. Glatiramer acetate reactive T-cells produce brain derived neurotrophic factor (BDNF). J Neurol Sci. 140:37-44, 2003.
7. Dhib-Jalbut, S., Chen, M., Said, A., Zhan, M., Johnson, K., Martin, R. Glatiramer acetate reactive blood mononuclear cells respond to multiple myelin antigens with a Th-2 biased phenotype. J Neuroimmunol. 140 :163-171, 2003.
8. Goolsby, J., Marty, M.C., Heletz, D., Chiappelli, J., Tashko, G., Yarnell, D., Fishman, P.S., Dhib-Jalbut, S., Bever, C.T. Jr, Pessac, B., Trisler, D. Hematopoietic progenitors express neural genes. Proc. Natl. Acad. Sci .U S A. 100:14926-14931, 2003.
9. Dhib-Jalbut, S. and Mouradian, M.M.. Delivery of therapeutic genes into the central nervous system using bone marrow cells as vehicles. Expert Opin. Biol. Ther. 4:669-675, 2004.
10. Graber, J., Zhan, M., Ford, D., Kursch, F., Francis, G., Bever, C., Panitch, H., Calabresi, PA., Dhib-Jalbut, S. Interferon-ß-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in multiple sclerosis. Journal of Neuroimmunology 161:169-176, 2005.
11. Huh, J., Yao, K., Quigley, L., McFarland, H.F., Muraro, P.A., Martin, R., and Ito, K.: Limited repertoire of HLA-DRB1*0401-restricted MBP111-129 specific T cells in HLA-DRB1*0401 Tg mice and their pathogenic potential. J. Neuroimmunol: 151, 94-102, 2004.
12. Quandt, J.A., Baig, M., Yao, K., Kawamura, K., Huh, J., Ludwin, S.K., Bian, H.J., Bryant, M., Quigley, L., Nagy, Z.A., McFarland, H.F., Muraro, P.A., Martin, R., and Ito, K. Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice. J Exp Med 200:223-234, 2004.