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Lipids as the key to understanding α-synuclein behaviour in Parkinson disease

Nature Reviews Molecular Cell Biology volume 21, pages 357–358 (2020)Cite this article

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Parkinson disease is a devastating neurodegenerative condition that is characterized by intraneuronal toxic assemblies of the α-synuclein protein. In this Comment, we discuss the emerging role of lipids in understanding biology as well as in the identification of new therapeutic targets in this disease.

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References

  1. Shahmoradian, S. H. et al. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat. Neurosci. 22, 1099–1109 (2019).

    Article  CAS  Google Scholar 

  2. Theillet, F. X. et al. Structural disorder of monomeric α-synuclein persists in mammalian cells. Nature 530, 45–50 (2016).

    Article  CAS  Google Scholar 

  3. Fusco, G. et al. Direct observation of the three regions in α-synuclein that determine its membrane-bound behaviour. Nat. Commun. 5, 3827 (2014).

    Article  CAS  Google Scholar 

  4. Galvagnion, C. et al. Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein. Proc. Natl Acad. Sci. USA 113, 7065–7070 (2016).

    Article  CAS  Google Scholar 

  5. Fusco, G. et al. Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers. Science 358, 1440–1443 (2017).

    Article  CAS  Google Scholar 

  6. Zunke, F. et al. Reversible conformational conversion of α-synuclein into toxic assemblies by glucosylceramide. Neuron 97, 92–107 (2018).

    Article  CAS  Google Scholar 

  7. Mazzulli, J. R. et al. Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146, 37–52 (2011).

    Article  CAS  Google Scholar 

  8. Henderson, M. X. et al. Glucocerebrosidase activity modulates neuronal susceptibility to pathological α-synuclein insult. Neuron 105, 822–836 (2019).

    Article  Google Scholar 

  9. Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat. Genet. 51, 414–430 (2019).

    Article  CAS  Google Scholar 

  10. Fanning, S. et al. Lipidomic analysis of α-synuclein neurotoxicity identifies stearoyl CoA desaturase as a target for Parkinson treatment. Mol. Cell 73, 1001–1014 (2019).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the Azrieli Foundation for the award of an Azrieli Fellowship and Marguerite Stolz Research Fellowship.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Roni Stok & Avraham Ashkenazi

  2. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    Avraham Ashkenazi

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  1. Roni Stok
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  2. Avraham Ashkenazi
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Correspondence to Avraham Ashkenazi.

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Stok, R., Ashkenazi, A. Lipids as the key to understanding α-synuclein behaviour in Parkinson disease. Nat Rev Mol Cell Biol 21, 357–358 (2020). https://doi.org/10.1038/s41580-020-0235-y

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