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alpha-Synuclein and intracellular trafficking: impact on the spreading of Parkinson’s disease pathology

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Abstract

Parkinson’s disease is characterized by intracellular proteinaceous depositions known as Lewy bodies. These largely consist of the protein α-synuclein, whose physiological function remains unclear, but mutations and overexpression of the protein have been shown to cause early onset cases of Parkinson’s disease. Deregulation of α-synuclein biology causes neurodegeneration and impaired neuronal trafficking, hinting at a possible contribution to the pathological mechanism. Recent studies produced some evidence hinting at the involvement of several regulators of the transport machinery such as Rab GTPases and SNARE proteins, but also shown that α-synuclein can be propagated between cells. Here, we discuss the molecular interplay of α-synuclein with the intracellular transport machinery, its consequences, and the implications for disease mechanisms.

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Acknowledgments

TFO is supported by the Cluster of Excellence and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain. We thank Catarina Fernandes for her excellent support with figure preparation.

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  1. Department for Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Waldweg 33, 37073, Göttingen, Germany

    Sibylle E. Eisbach & Tiago F. Outeiro

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  1. Sibylle E. Eisbach
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  2. Tiago F. Outeiro
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Correspondence to Tiago F. Outeiro.

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Eisbach, S.E., Outeiro, T.F. alpha-Synuclein and intracellular trafficking: impact on the spreading of Parkinson’s disease pathology. J Mol Med 91, 693–703 (2013). https://doi.org/10.1007/s00109-013-1038-9

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  • DOI: https://doi.org/10.1007/s00109-013-1038-9

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