Center for Neurodegenerative and Neuroimmunologic Diseases

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 in PD include the conduct of basic research in the molecular pathogenesis of the disease with a focus on the role of genetic mutations in protein aggregation and neuronal cell death, the identification of targets for therapeutic interventions, and testing those targets in animal models. In MS, research projects focus on immunopathogenesis using animal models, mechanisms of action of MS therapies, 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 graduate students, post-doctoral fellows and physician scientists in neurodegenerative and neuroimmunological diseases, and to provide elective time for undergraduates, medical students, and neurology residents or trainees from other departments who wish to explore research opportunities in neurologic diseases.

Faculty:

• M. Maral Mouradian, MD, Center Director, William Dow Lovett Professor of Neurology
• Suhayl Dhib-Jalbut, MD, Professor and Chairman, Department of Neurology
• Konstantin E. Balashov, MD, PhD, Associate Professor of Neurology
• Eunsung Junn, PhD, Assistant Professor of Neurology
• Kouichi Ito, PhD, Assistant Professor of Neurology

Postdoctoral Fellows:

• Sridhar Boppana, PhD
• Yoon-Jee Chae, PhD
• Doo-Chul Choi, PhD
• Liqiang He, PhD
• Jong-Min Woo, PhD

Graduate Student:

• Hilary Grosso, (PhD 2012)

Research Specialists:

• Naoko Ito, BS
• Latt Latt Aung, MD

Administrative Staff:

• Sheila Reaves - Program Support Specialist

Selected recent publications from the Center:

Yang Y, Hwang CK, D'Souza UM, Lee SH, Junn E, and Mouradian MM . Three-amino Extension Loop Homeodomain Proteins Meis2 and TGIF Differentially Regulate Transcription. J. Biol. Chem. 275(27):20734-2074, 2000.

Junn E, Han SH, Im JY, Cho EW, Um HD, Kim DK, Lee KW, Han PL, Rhee SG and Choi I. Vitamin D3 Up-Regulated Protein 1 Mediates Oxidative Stress Via Suppressing the Thioredoxin Function. J. Immunol. 164(12):6287-6295, 2000.

Waragai M, Junn E, Kajikawa M, Takeuchi S, Kanazawa I, Shibata M, Mouradian MM, Okazawa H. PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15kD/dim1p via the carboxyl-terminal domain. Biochem Biophys Res Commun. 273(2):592-5, 2000. (Co-First Author)

Junn E, Lee KN, Ju HR, Han SH, Im JY, Kang HS, Lee TH, Bae YS, Ha KS, Lee ZW, Rhee SG, and Choi I, Requirement of Hydrogen Peroxide Generation in TGF-beta1 Signal Transduction in Human Lung Fibroblast Cells: Involvement of Hydrogen Peroxide and Ca2+ in TGF-beta1-Induced IL-6 Expression. J Immunol. 165(4):2190-2197, 2000.

Yang Y, Hwang CK, Junn E, Lee G, and Mouradian MM. ZIC2 and Sp3 Repress Sp1-Induced Activation of the Human D1A Dopamine Receptor Gene. J. Biol. Chem. 275(49): 38863-38869, 2000.

Junn E and Mouradian MM. Apoptotic signaling in Dopamine-induced Cell Death: The Role of Oxidative Stress, p38 Mitogen-Activated Protein Kinase, Cytochrome c and Caspases. J. Neurochem. 78(2): 374-383, 2001.

Junn E and Mouradian MM. Human a-Synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neuroscience Lett. 320: 146-150, 2002.

Lee G, Junn E, Tanaka M, Kim YM, Lee SS, and Mouradian MM. Synphilin-1 degradation by the ubiquitin-proteasome pathway and effects on cell survival. J. Neurochem. 83(2): 346-352, 2002 (Co-First Author).

Han KG, Kim DH, Junn E, Lee SS, and Kang C. Identification of Bacteriophage K11 Genomic Promoters for K11 RNA Polymerase. J. Biochem. Mol. Biol. 35(6): 637-641, 2002.

Junn E, Lee SS, Suhr UT and Mouradian MM. Parkin Accumulation in Aggresomes due to Proteasome impairment. J. Biol. Chem., 277(49): 47870-47877, 2002.

Lee, G., Junn, E., Tanaka, M., Kim, Y.M., Lee, S.S., Mouradian, M.M.: Synphilin-1 degradation by the ubiquitin- proteasome pathway and effects on cell survival. J. Neurochem., 83:346-352, 2002.

Junn, E., Mouradian, M.M.: Human a-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci. Lett., 320:146-150, 2002.

Dunah, A.W., Jeong, H., Griffin, A., Kim, Y.-M., Hersch, S.M., Mouradian, M.M., Young, A.B., Tanese, N., Krainc, D.: Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science, 296:2238-2243, 2002.

Junn E, Ronchetti RD, Quezado MM, Kim SY, Mouradian MM.. Tissue transglutaminase- induced aggregation of {alpha}-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.

Lee SS, Kim YM, Junn E, Lee G, Park KH, Tanaka M, Ronchetti RD, Quezado MM, Mouradian MM. Cell cycle aberration by a-Synuclein over-expression and cyclin B immunoreactivity in Lewy bodies. Neurobiology of Aging, 24(5): 687-696, 2003.

Junn, E., Ronchetti, R.D., Quezado, M.M., Kim, S.-Y., Mouradian, M.M.: Tissue transglutaminase-induced aggregation of a-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.

Blanchet, P.J., Konitsiotis, S., Mochizuki H., Pluta, R., Emerich, D.F., Chase, T.N., Mouradian, M.M.: Complications of a trophic xenotransplant approach in parkinsonian monkeys. Prog. Neuropsychopharmacol. Biol. Psychiatry, 27(4):607-612, 2003.

Quandt J.A., Baig M., Yao K., Kawamura K, Huh J., Ludwin S., Bian H.J., Bryant M., Quigley L., Nagy Z., McFarland H.F., Muraro P.A., Martin R., and Ito K. Unique Phenotypic Clinical and Pathological Features in HLA-DRB1*0401-restricted MBP111-129-specific Humanized TCR Tg mice. J. Exp. Med. 2004; 200: 223-234. 

Huh J., K. Yao, L. Quigley, 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. 2004; 151: 94-102.

Tanaka M, Kim YM, Lee G, Junn E, Iwatsubo T and Mouradian MM. Aggresomes formed by a-Synuclein and Synphilin-1 are cytoprotective. J. Biol. Chem,. 279(6): 4625-4631, 2004.

Lee G, Tanaka M, Park K, Lee SS, Kim YM, Junn E Lee SH and Mouradian MM. Casein kinase II phosphorylation regulates Synphilin-1/a-Synuclein interaction and inclusion body formation. J. Biol. Chem., 279(8): 6834-6839, 2004.

Makar, T.K., Trisler, D., Eglitis, M.A., Mouradian, M.M., Dhib-Jalbut, S.: Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles. Neurosci. Lett. 356:215-219, 2004.

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 a-synuclein / synphilin-1 interaction and inclusion body formation. J. Biol. Chem., 279(8):6834-6839, 2004.

Dhib-Jalbut, S., Mouradian, M.M.: Delivery of transgenically modified adult bone marrow cells to the rodent central nervous system. Expert Opin. Biol. Th., 4(5):669-675, 2004.

Junn E, Taniguchi H, Jeong BS, Zhao X, Ichijo H and Mouradian MM. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase activity and cell death. Proc. Natl. Acad. Sci. USA. 102(27): 9691-9696, 2005.

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.

Gebe JA, Unrath KA, Falk BA, Ito K., Wen L, Daniels TL, Lernmark A, and Nepom GT. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice. Clin. Immunol. 2006;121: 294-304.

Graber J, Ford D, Zhan M, Francis G, Panitch H, Dhib-Jalbut S. Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlation with interferon dose and MRI response. J. Neuroimmunology, 185:168-74, 2007.

Valenzuela R, Costello K, Johnson KP, Dhib-Jalbut S. Ex-Vivo cellular IL-4/IFN-gamma correlates with clinical response to Glatiramer acetate in multiple sclerosis. Multiple Sclerosis 13:754-762, 2007.

Suhayl Dhib-Jalbut, MD Pathogenesis of Myelin/Olgodendrocyte damage in Multiple Sclerosis. Neurology 2007;68(suppl3):S13-S21.

Park KA, Byun HS, Won M, Yang KJ, Shin S, Piao L, Kim JM, Woon WH, Junn E, Park J, Seok JH, Hur GM. Sustained activation of protein kinase C down-regulates nuclear factor-{kappa}B signaling by dissociation of IKK-{gamma} and Hsp90 complex in human colonic epithelial cells. Carcinogenesis 28(1): 71-80, 2007.

Kawamura K.,  Yao K., Shukaliak-Quandt JA , Huh J.,  Baig M., Quigley L., Ito N., Necker A.,  McFarland HF,  Muraro PA, Martin R, and Ito K. Different development of MBP agonist- and antagonist-specific human TCR Tg T cells in the thymus and periphery. J. Immunology 2008; 181(8): 5462-72.

Tapas K. Makar, David Trisler, Christopher T. Bever, James E. Goolsby, Karna T. Sura,, Shailesh Balasubramanian, Shireen Sultana, Niraj Patel, David Ford, Ishwar S. Singh, Aditi Gupta*, Reuben M. Valenzuela, Suhayl Dhib-Jalbut.  Stem cell-based delivery of IFN-B reduces relapses in Experimental Autoimmune Encephalomyelitis. J Neuroimmunology, 196:67-81, 2008.

Ryu, M.Y., Kim, D.W., Arima, K., Mouradian, M.M., Kim, S.U., Lee, G.. Localization of CKII b subunits in Lewy bodies of Parkinson's disease. J. Neurol. Sci., 266:9-12, 2008.

Mochizuki, H., Yasuda, T., Mouradian, M.M.: Advances in gene therapy for movement disorders. Neurotherapeutics, 5(2):260-269, 2008.

Lee. S.H., Jang, M.K., Lee, O.H., Ok Soo Kim, Kim, Y.-M., Yajima, S., Lee, Y.-C., Mouradian, M.M.: Transcriptional auto-regulation of the dopamine receptor regulating factor (DRRF) gene. Mol. Cell. Endocrinol. 289:23-28, 2008.

Makar T, Bever C, Singh I, Royal W, Sahu S, Sura T, Sultana S, Sura K, Patel N, Dhib-Jalbut S, Trisler D. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow cells as a vehicle. J. Neuroimmunology, 210:40-51, 2009.

Balashov KE, Aung LL, Dhib-Jalbut S, Keller IA. Acute Multiple Sclerosis Lesion: Conversion of restricted diffusion due to vasogenic edema. J Neuroimaging, Nov 3, 2009.

Freedman M, Cohen B, Dhib-Jalbut S, Jeffrey D, Reder A, Sandberg-Wolheim M, Weinstock-Guttman B. Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command. Current Medical Research & Opinion, 25:2459-2470, 2009.

Junn E, Jang WH, Zhao X, Jeong BS and Mouradian MM. Mitochondrial Localization of DJ-1 Leads to Enhanced Neuroprotection. J. Neurosci. Res. 87(1): 123-129, 2009.

Junn E, Lee KW, Jeong BS, Chan TW, Im JW and Mouradian MM. Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc. Natl. Acad. Sci. USA. 106(31):13052-7, 2009.

Lee, S.H., Jang, M.K., Kim, O.S., Lee, O.H., Kim, N.Y., Yoo, K.H., Lee, D.G., Shong, Y.H., Mouradian, M.M.: Activation of the GDNF-Inducible Transcription Factor (GIF) Gene Promoter by Glucocorticoid and Progesterone. J. Steroid Biochem. Mol. Biol., 115(1-2):30-35, 2009.

Graber J, Dhib-Jalbut S. Protective immunity in the nervous system. Pharmacology & Therapeutics, 121:147-59, 2009.

Balashov, K.E., Pal, G., and M.L. Rosenberg. Optic neuritis incidence is increased in spring months in patients with asymptomatic demyelinating lesions. Multiple Sclerosis 2010; 16: 252-4 (PMCID:PMC2861653)

Aung, L.L., Fitzgerald-Bocarsly, P., Dhib-Jalbut, S., and K. E. Balashov, Plasmacytoid dendritic cells in multiple sclerosis: Chemokine and chemokine receptor modulation by interferon-beta. J Neuroimmunol 2010, 226(1-2):158-64 (PMCID: PMC2937086)

Meier, D.S., Balashov, K., Healy, B.C., Weiner, H.L., and C.R.G.  
Guttmann.   Seasonal prevalence of MS disease activity. Neurology 2010; 75: 799–806 (PMCID: PMC2938966).

Balashov,K.E., Aung, L.L., Vaknin-Dembinsky, A., Dhib-Jalbut, S., Weiner, H.L. Interferon-beta inhibits Toll-like receptor 9 processing in multiple sclerosis. Ann Neurol 2010; 68: 899-906. (PMCID: PMC3058378)

Dhib-Jalbut S, Marks S. Interferon-B mechanisms of action in multiple sclerosis. Neurology 74:S17-24, 2010.

Dhib-Jalbut S. Guest Editor, Multiple Sclerosis Disease-Modifying Therapies: Mechanisms of Action and Practical Implications. Neurology, V74, Supplement 1, 2010.

Graber J, McGraw CA, Kimbrough D, Dhib-Jalbut S. Overlapping and distinct mechanisms of action of multiple sclerosis therapies. Clinical Neurology and Neurosurgery. Clin Neurol Neurosurg. 2010 Sep;112(7):583-91.

Im JY, Lee KW, Junn E and Mouradian MM. DJ-1 Protects Against Oxidative Damage by Regulating the Thioredoxin/ASK1 Complex. Neuroscience Res. 67(3): 203-8, 2010.

Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, Junn E and Kim HS. a-Synuclein Activates Microglia by Inducing the Expressions of Matrix Metalloproteinases and the Subsequent Activation of Protease-Activated Receptor-1. J. Immunol. 185(1): 615-23, 2010.

Junn, E., Mouradian, M.M.: microRNAs in neurodegenerative disorders. Cell Cycle, 9(9):1717-1721, 2010.

Cao, X., Yasuda, T., Uthayathas, S., Ray L. Watts, R.L., Mouradian, M.M., Mochizuki, H., Papa, S.M.: Striatal overexpression of DeltaFosB reproduces chronic levodopa-induced involuntary movements. J. Neurosci., 30(21):7335-7343, 2010.

Balashov, K.E., Aung L., Dhib-Jalbut S., and I.A. Keller. Acute multiple sclerosis lesion: Conversion of restricted diffusion due to vasogenic edema. J Neuroimaging 2011; 21: 202-4. (PMCID: PMC2891920).

Longhini, A.L.F., Glehn, F., Brand√£o, C.O., dePaula, R.F.O., Pradella, F., Moraes. A.S., Farias, A.S., Oliveira, E.C., Quispe-Cabanillas, J.G., Abreu, C.H., Damasceno, A., Damasceno, B.P., Balashov, K.E., and L.M.B. Santos. Plasmacytoid Dendritic Cells are increased in Cerebrospinal Fluid of Untreated Patients during Multiple Sclerosis Relapse. J Neuroinflammation 2011; 8 (2): 1-4. (PMCID: PMC3022734)

Boppana S, Huang H, Ito K, Dhib-Jalbut S. Immunologic aspects of multiple sclerosis. Mount Sinai Journal of Medicine 78:207-220, 2011.

Graber J and Dhib-Jalbut S. Biomarkers in Multiple Sclerosis. J Neurological Sciences 305:1-10, 2011.

Lee K-W, Chen W, Junn E, Im J-Y, Grosso H, Sonsalla PK, Feng X, Ray N, Fernandez JR, Chao Y, Masliah E, Voronkov M, Braithwaite SP, Stock JB and Mouradian MM. Enhanced phosphatase activity attenuates alpha-synucleinopathy in a mouse model. J. Neurosci. 31(19):6963-71, 2011

Kim YM, Jang WH, Quezado MM Oh Y, Chung KC, Junn E and Mouradian MM. Proteasome inhibition induces a-Synuclein SUMOylation and Aggregate formation. J. Neurological Sciences 307(1-2):157-61, 2011.

Junn E and Mouradian MM. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol Ther. 133(2):142-50, 2011. (Corresponding author)

Oh, Y., Kim, Y.M., Mouradian, M.M., Chung, K.C.: Human Polycomb protein 2 promotes a-synuclein aggregate formation through covalent SUMOylation. Brain Res., 1381:78-89, 2011.

Balashov, K.E. and E. Lindzen. Acute demyelinating lesions with restricted diffusion in multiple sclerosis. Multiple Sclerosis Journal, published online before print, April 20, 2012. doi: 10.1177/1352458512445407.

Aung L.L, Brooks, A., Greenberg, S.A., Rosenberg, M.L., Dhib-Jalbut, S., and K.E. Balashov. Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells. J Neuroimmunol 2012. Accepted for publication, doi: 10.1016/j.jneuroim.2012.05.013.

Lee KW, Zhao X, Im JY, Grosso H, Jang WH, Chan TW, Sonsalla PK, German DC, Ichijo H, Junn E, Mouradian MM. Apoptosis Signal-Regulating Kinase 1 Mediates MPTP Toxicity and Regulates Glial Activation. PLoS One. 2012;7(1):e29935.

Junn, E., Mouradian, M.M.: MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol. Therap., 133(2):142-150, 2012.

Mouradian, M.M.: MicroRNAs in Parkinson's disease. Neurobiol. Dis., 46:279-284, 2012.

Grosso, H., Mouradian, M.M.: Transglutaminase 2: Biology, relevance to neurodegenerative diseases and therapeutic implications. Pharmacol. Therap., 133(3):392-410, 2012.

Braithwaite, S.P., Stock, J.B., Mouradian, M.M.: a-Synuclein phosphorylation as a therapeutic target in Parkinson's disease. Rev. Neurosci., 23(2):191-198, 2012.

Braithwaite, S.P., Voronkov, M., Stock, J.B., Mouradian, M.M.: Targeting phosphatases as the next generation of therapeutics for neurodegenerative disorders. Neurochem. Int., Epub ahead of print, February 8, 2012.

Im JY, Lee KW, Woo JM, Junn E, Mouradian MM. DJ-1 induces thioredoxin 1 expression through Nrf2 pathway. Hum. Mol. Genet., 21(13):3013-3024, 2012. PMID: 22492997.