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. Author manuscript; available in PMC: 2019 Jan 3.
Published in final edited form as: Neuron. 2017 Dec 28;97(1):92–107.e10. doi: 10.1016/j.neuron.2017.12.012

Figure 8. Schematic Diagram Summarizing the Effects of GSLs on α-Syn Aggregation.

Figure 8

In healthy human midbrain neurons, α-Syn exists as both physiological monomers and HMW conformers. GSLs such as GluCer preferentially act on HMW conformers, and to a minor extent on monomers, to convert them into assembly-state oligomers (AOs) with molecular radius that is identical to HMW physiological conformers. HMW physiological species are non-toxic, loosely self-associated species and can be directly converted into AOs. AOs are cytotoxic, compact, and PK resistant, and can accelerate the formation of assembled amyloid fibrils from free monomers.