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Mechanistic aspects of Parkinson’s disease: α-synuclein and the biomembrane

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Abstract

A key feature in Parkinson’s disease is the deposition of Lewy bodies. The major protein component of these intracellular deposits is the 140-amino acid protein α-synuclein that is widely distributed throughout the brain. α-synuclein was identified in presynaptic terminals and in synaptosomal preparations. The protein is remarkable for its structural variability. It is almost unstructured as a monomer in aqueous solution. Self-aggregation leads to a variety of β-structures, while membrane association may result in the formation of an amphipathic helical structure. The present article strives to give an overview of what is currently known on the interaction of α-synuclein with lipid membranes, including synthetic lipid bilayers, membraneous cell fractions, synaptic vesicles and intact cells. Manifestations of a functional relevance of the α-synuclein–lipid interaction will be discussed and the potential pathogenicity of oligomeric α-synuclein aggregates will be briefly reviewed.

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Acknowledgements

I thank Drs. Christian Haass and Frits Kamp for helpful comments on the manuscript. The author was supported by the Deutsche Forschungsgemeinschaft, SFB 596, TP 10.

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  1. Laboratory of Alzheimer’s and Parkinson’s Disease Research, Department of Biochemistry, Ludwig Maximilian University, 80336, Munich, Germany

    Klaus Beyer

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Beyer, K. Mechanistic aspects of Parkinson’s disease: α-synuclein and the biomembrane. Cell Biochem Biophys 47, 285–299 (2007). https://doi.org/10.1007/s12013-007-0014-9

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