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Dopamine cannot promote oligomerization of unoxidized <i>α</i>-synuclein
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
Division of Agriculture and Agricultural Life Sciences, The University of Tokyo, Tokyo, Japan
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 1 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- 2 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- 3 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- 4 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- 5 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 6 Division of Agriculture and Agricultural Life Sciences, The University of Tokyo, Tokyo, Japan
- 7 School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 8 School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 9 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
- 10 School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
- 11 School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan
- 12 Department of Chemistry, School of Sciences and Engineering, Meisei University, Tokyo, Japan
Journal of Biophysical Chemistry·Volume 04 (2013)·Pages 110–114·Published 9 August 2013·DOI10.4236/jbpc.2013.43015
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Abstract
α -Synuclein is the major component of the filamentous Lewy bodies and Lewy neurites that define neuropathological features of Parkinson’s disease and dementia with Lewy bodies. To investigate the oligomerization process of α -synuclein in association with dopamine (DA), the structural propensities to form oligomers were studied using NMR and other biophysical techniques. The 1 H- 15 N HSQC spectra indicated that both N- and C-termini interacted with DA. Although interactions with DA were also observed in the presence of glutathione by ESI-MS, the significant suppression of oligomerization was observed in the size exclusion chromatography, suggesting that oxidations of α -synuclein are required for its oligomerization.
Keywords<i>α</i>-SynucleinDopamineGlutathioneOligomerization
- Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D.A., Kondo, J., Ihara, Y. and Saitoh, T. (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proceedings of the National Academy of Sciences of USA, 90, 11282-11286. doi:10.1073/pnas.90.23.11282
- Weinreb, P.H., Zhen, W., Poon, A.W., Conway, K.A. and Lansbury, P.T. (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry, 35, 13709-13715. doi:10.1021/bi961799n
- Davidson, W.S., Jonas, A., Clayton, D.F. and George, J.M. (1998) Stabilization of α-synuclein secondary structure upon binding to synthetic membranes. The Journal of Biological Chemistry, 273, 9443-9449. doi:10.1074/jbc.273.16.9443
- George, J.M., Jin, H., Woods, W.S. and Clayton, D.F. (1995) Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron, 15, 361-372. doi:10.1016/0896-6273(95)90040-3
- Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., De Silva, H.A., Kittel, A. and Saitoh, T. (1995) The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron, 14, 467-475. doi:10.1016/0896-6273(95)90302-X
- Ma, Q.L., Chan, P., Yoshii, M. and Uéda, K. (2003) Alpha-synuclein aggregation and neurodegenerative diseases. Journal of Alzheimer’s Disease, 5, 139-148.
- Yu, S., Li, X., Liu, G., Han, J., Zhang, C., Li, Y., Xu, S., Liu, C., Gao, Y., Yang, H., Uéda, K. and Chan, P. (2007) Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience, 145, 539-555. doi:10.1016/j.neuroscience.2006.12.028
- Conway, K.A., Rochet, J.C., Bieganski, R.M. and Lansbury, P.T. Jr. (2001) Kinetic stabilization of the alpha-synucleinprotofibril by a dopamine-alpha-synuclein adduct. Science, 294, 1346-1349. doi:10.1126/science.1063522
- Pham, C.L.L., Leong, S.L., Ali, F.E., Kenche, V.B., Hill, A.F., Gras, S.L., Barnham, K.J. and Cappai, R. (2009) Dopamine and the dopamine oxidation product 5,6-dihydroxylindole promote distinct on-pathway and off-pathway aggregation of alpha-synuclein in a pH-dependent manner. Journal of Molecular Biology, 387, 771-785. doi:10.1016/j.jmb.2009.02.007
- Rekas, A., Knott, R.B., Sokolova, A., Barnham, K.J., Perez, K.A., Masters, C.L., Drew, S.C., Cappai, R., Curtain, C.C. and Pham, C.L.L. (2010) The structure of dopamine induced α-synuclein oligomers. European Biophysics Journal, 39, 1407-1419. doi:10.1007/s00249-010-0595-x