| Faculty
Profile |
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M.
Maral Mouradian , M.D.
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William
Dow Lovett Professor MD 1982, American University of Beirut |
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| Director,
Center for Neurodegenerative and Neuroimmunologic Diseases (732) 235 -
4772
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| Research Interests | Research Techniques | |
| Molecular pathogenesis and therapeutic interventions in Parkinson's disease |
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Research Summary |
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| Our research focus is to elucidate the molecular
events that lead from genetic mutations in Parkinson’s disease
to neuronal degeneration with the objective of identifying targets
that can be interdicted for therapeutic intent. Several different
genes have already been identified in this disorder some dominantly
inherited gain of function mutations and others recessive loss of
function mutations. Using cellular and molecular techniques in both
mammalian and yeast cells as well as genetically modified mice,
the impact of these disease-associated genes are investigated. For
example, point mutations or multiplication of the gene encoding
α-synuclein is linked to dominantly inherited Parkinson's. Pathologic
misfolding of this protein is believed to be toxic to neurons. We
have identified a factor that promotes this process and are testing
pharmacological approaches to mitigate it. Another example is the
gene encoding DJ-1. We have found a novel death signaling pathway
that is blocked by wild-type DJ-1, a function that is lost by pathogenic
mutation. Ongoing studies address this pathway in mice. |
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Key References |
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For complete list: PubMed Junn, E., Jang, W.H.,
Zhao, X., Jeong, B.S., and Mouradian, M.M. (2008) Mitochondrial
localization of DJ-1 leads to enhanced neuroprotection. Junn, E., Taniguchi. H., Jeong, B.S., Zhao, X., Ichijo, H., Mouradian, M.M. (2005) Interaction of DJ-1 with Daxx inhibits ASK1 activity and cell death. PNAS 102: 9691-9696 Tanaka, M., Kim, Y.M., Lee, G., Junn, E., Iwatsubo, T., Mouradian, M.M. (2004) Aggresomes formed by α-synuclein and synphilin-1 are cytoprotective. J. Biol. Chem., 279:4625-4631 Lee, G., Tanaka, M., Park, K., Lee, S.S., Kim, Y.M., Junn, E., Lee, S.H., Mouradian, M.M. (2004) Casein kinase II mediated phosphorylation regulates α-synuclein / synphilin-1 interaction and inclusion body formation. J. Biol. Chem. 279:6834-6839 Junn, E., Ronchetti, R.D., Quezado, M.M., Kim, S.-Y., Mouradian,
M.M. (2003): Tissue transglutaminase-induced aggregation
of alpha-synuclein: Implications for Lewy body formation in Parkinson’s
disease and dementia with Lewy bodies. PNAS 100:2047-2052 |
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