About Dr. Yoon-Seong Kim, MD
Elucidate the molecular mechanism underlying the pathogenesis of Parkinson's disease. Current focus is on DNA oxidative damage and its contribution to mutated α-syn through transcriptional mutagenesis.
My research explores the molecular mechanism underlying selective degeneration of the specific neuronal population in neurodegenerative disorders, especially Parkinson’s disease (PD).
Although oxidative stress is considered as a major contributing factor in PD, molecular sources for ROS in PD remain poorly understood. Emerging evidence has demonstrated that NADPH oxidases, the specialized superoxide generating enzyme complex, play a key role in oxidative stress in various disease conditions in the central nervous system. We recently discovered that the NADPH oxidase 1 (NOX1)/Rac1 system is activated in dopaminergic neurons under various stress conditions and plays a key role in oxidative stress-mediated dopaminergic neuronal degeneration. Mutations in Leucine-rich-repeat-kinase 2 (LRRK2), a newly identified causative gene for PD, also increase Nox1 expression and ROS generation in DA cells. Together, our findings suggest that Nox1-derived superoxide generation in DA neurons is likely a common downstream event in idiopathic or genetic causes of PD. This research is currently supported by NIH and Michael J. Fox foundation.
Recently, our lab has established paraquat-based rat PD model in which significant dopaminergic neuronal degeneration as well as alpha-synuclein aggregation, a key pathologic feature, are successfully observed. Using this novel animal model, our lab members are trying to discover the molecular mechanism governing Nox1/Rac1-derived oxidative stress in the nigrostriatal pathway and its effect on the genome-wide epigenetic regulation in PD.
To efficiently achieve this research goals, my lab have established a number of important tools including adeno-associated viral (AAV) gene targeting and expression in vivo, real-time imaging of ROS generation in neurons, oxidative changed DNA immunoprecipitation (oxo-DIP) and target gene specific methyl-profiling.
- Campos, F. L., Carvalho, M. M., Cristovão, A. C., Je, G., Baltazar, G., Salgado, A. J., Kim, Y.-S., and Sousa, N. (2013) Rodent models of Parkinson’s disease: beyond the motor symptomatology. Frontiers in Behavioral Neuroscience 7, 175
- Chung, Y. C., Kim, Y.-S., Bok, E., Yune, T. Y., Maeng, S., and Jin, B. K. (2013) MMP-3 Contributes to Nigrostriatal Dopaminergic Neuronal Loss, BBB Damage, and Neuroinflammation in an MPTP Mouse Model of Parkinson’s Disease. Mediators of Inflammation 2013
- Cristóvão, A. C., Barata, J., Je, G., and Kim, Y.-S. (2013) PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons. Biochemical and biophysical research communications 437, 380-385
- Lee, K., Im, J., Woo, J., Grosso, H., Kim, Y., Cristovao, A., Sonsalla, P., Schuster, D., Jalbut, M., and Fernandez, J. (2013) Neuroprotective and Anti-inflammatory Properties of a Coffee Component in the MPTP Model of Parkinson’s Disease. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics
- Choi DH, Cristóvão AC, Guhathakurta S, Lee J, Joh TH, Beal MF, Kim YS (2012) NADPH Oxidase 1-Mediated Oxidative Stress Leads to Dopamine Neuron Death in Parkinson’s Disease. Antioxid Redox Signal. 16, 1033-1045
- Choi DH, Kim YJ, Kim YG, Joh TH, Beal MF, Kim YS (2011) Role of matrix metalloproteinase 3-mediated alpha-synuclein cleavage in dopaminergic cell death. J Biol Chem 286, 14168-77
- Choi DH, Hwang O, Lee KH, Lee J, Beal F. and Kim YS (2010) DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidative stress induced dopaminergic cell death. Antioxid Redox Signal 14, 2137-50.
- Cho Y, Son HJ, Kim EM, Choi JH, Kim ST, Ji IJ, Choi DH, Joh TH, Kim YS, Hwang O (2009) Doxycycline is Neuroprotective Against Nigral Dopaminergic Degeneration by a Dual Mechanism Involving MMP-3. Neurotox Res 16, 361-71
- Cristóvão AC, Choi DH, Baltazar G, Beal MF and Kim YS (2009) The role of NADPH oxidase-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal 11, 2105-18