Effect of amyloid oligomerization on alpha-synuclein curvature-membrane sensitivity.

JAMESON DM; MAS C; CELEJ MS; AMBROGGIO EE; JAMES NG; GALLEA JI

Congreso; Reunión conjunta de Sociedades de Biociencias; 2017

The protein alpha-synuclein (AS) is as a critical regulator of synaptic vesicle αdynamics in dopaminergic neurons. Te amyloid aggregation of AS is pathognomonicof Parkinson?s disease, a movement disorder associated with axon degeneration ofdopaminergic nigral neurons. In this context, prefbrillar oligomeric species are pointedas highly neurotoxic. AS has a greater afnity for highly curved vesicles, such as that ofsynaptic vesicles. Here, we investigated the loss-of-function that might be associated tothe conversion of AS from its monomeric functional state to its pathological oligomericform by evaluating the impact of AS oligomerization on its membrane-curvaturesensitivity. We used Fluorescence Correlation Spectroscopy to determine AS bindingafnity to membranes varying in sizes and compositions. We found thatoligomerization abolishes AS binding to physiological-like membranes and changescurvature-sensitivity towards neutral membranes. Our fndings provide insight intohow amyloid oligomerization can modulate AS physiopathology.