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J Biol Chem. 2019 May 7. pii: jbc.REV119.007500. doi: 10.1074/jbc.REV119.007500. [Epub ahead of print]

The role of lipids in α-synuclein misfolding and neurotoxicity.

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La Trobe University, Australia.
Pathology, The University of Melbourne, Australia.
Florey Institute of Neuroscience and Mental Health, Australia.
Biochemistry and Genetics, La Trobe University, Australia.


The misfolding and aggregation of α-synuclein (αsyn) in the central nervous system is associated with a group of neurodegenerative disorders referred to as the synucleinopathies. In addition to being a pathological hallmark of disease, it is now well established that upon misfolding αsyn acquires pathogenic properties, such as neurotoxicity, that can contribute to disease development. The mechanisms that produce αsyn misfolding and the molecular events underlying the neuronal damage caused by these misfolded species are not well defined. A consistent observation that may be relevant to αsyn's pathogenicity is its ability to associate with lipids. This appears important not only to how αsyn aggregates, but also to the mechanism by which the misfolded protein causes intracellular damage. This review discusses the current literature reporting a role of lipids in αsyn misfolding and neurotoxicity in various synucleinopathy disorders, and provides an overview of current methods to assess protein misfolding and pathogenicity both in vitro and in vivo.


Parkinson disease; alpha-synuclein (a-synuclein); lipid; neurodegenerative disease; protein misfolding

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