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Demonstration of three dopamine molecules bound to α-Synuclein: Implication of oligomerization at the initial stage

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DOI: 10.4236/jbpc.2012.32017    3,115 Downloads   5,828 Views   Citations

ABSTRACT

α-Synuclein is the major component of the filamentous Lewy bodies and Lewy neurites that define neuropathological features and dementia with Lewy bodies. To investigate the role of dopamine (DA) in α-synuclein fibrillation, the structural propensities to form oligomers at the initial stage fibrillation were studied using size exclusion chromatography and various biophysical techniques. Interactions with DA were observed for wild-type α-synuclein and its mutants, A30P, E46K and A53T, using electrospray ionization mass spectrometry (ESI-MS). The results of ESI-MS indicate that an intact α-synuclein, which was not oxidized, had an ability to bind with three molecules of DA at the initial stage. Furthermore, upon binding to DA, α-synuclein oligomerizes to higher molecular weight species. These oligomers are structurally different from amyloid fibrils, as confirmed by thioflavin T and CD analysis.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Shimotakahara, S. , Shiroyama, Y. , Fujimoto, T. , Akai, M. , Onoue, T. , Seki, H. , Kado, S. , Machinami, T. , Shibusawa, Y. , Uéda, K. and Tashiro, M. (2012) Demonstration of three dopamine molecules bound to α-Synuclein: Implication of oligomerization at the initial stage. Journal of Biophysical Chemistry, 3, 149-155. doi: 10.4236/jbpc.2012.32017.

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