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Molecular Understanding of Copper and Iron Interaction with α-Synuclein by Fluorescence Analysis

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Abstract

α-Synuclein aggregation is a hallmark pathological feature in Parkinson’s disease (PD). The conversion of α-synuclein from a soluble monomer to an insoluble fibril may underlie the neurodegeneration associated with PD. Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance α-synuclein fibrillogenesis. In the present investigation, we analyzed the binding efficiency of Cu and Fe to α-synuclein by fluorescence studies. It is interesting to note that Cu and Fe showed differential binding pattern toward α-synuclein (wild type and A30P, A53T, and E46K mutant forms) as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. The experimental data might prove useful in understanding the hierarchy of metals binding to α-synuclein and its role in neurodegeneration.

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Acknowledgments

The authors are indebted to Dr. V. Prakash, Director, Central Food Technological Research Institute, Mysore for his support and encouragement. The authors profoundly thankful to Dr. Rivka Ravid, Senior Advisor, The Netherlands Academy of Science and Netherlands Brain Bank, The Netherlands for reviewing the manuscript and providing constructive comments. The authors thank Prof. Raghavan Varadarajan, Molecular Biophysics Unit, Indian Institute of Science, Bangalore for providing the facility. Bharathi is thankful to Council for Scientific and Industrial Research for awarding senior research fellowship. This work was supported by a grant from Department of Atomic Energy, through BNRS project, Mumbai, India.

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  1. K. S. J. Rao

    Present address: Department of Neurosciences, Medical University of South Carolina, Ashley Avenue, Charleston, SC, 29425, USA

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  1. Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, 570020, India

    Bharathi & K. S. J. Rao

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Bharathi, Rao, K.S.J. Molecular Understanding of Copper and Iron Interaction with α-Synuclein by Fluorescence Analysis. J Mol Neurosci 35, 273–281 (2008). https://doi.org/10.1007/s12031-008-9076-4

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