Effect of amyloid oligomerization on alfa-synuclein curvature-membrane sensitivity

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

Congreso; 19th IUPAB Congress & 11th EBSA Congress; 2017

Parkinson?sdisease (PD) is a neurodegenerative movement disorder associated with axondegeneration of dopaminergic nigral neurons. The cardinal pathological of PD,is the presence of proteinaceous highly organized fibrillar inclusions, termedLewy bodies, the main component of which is the 140 aa protein a-synuclein(AS). In addition, a number of prefibrillarintermediates have been associated with PD pathology. These oligomers have beenpointed as the most toxic species and they are more likely located in axons andpresynaptic terminals where they might damage synapses and dendrites. Functionally,AS assists in the regulation of the distal reserve pool of synaptic vesicleswhere protein/membrane interactions would help to dock these vesicles in aregion distal from the synapsis. Among the several membrane properties thatmodulate AS binding, curvature plays a key role. The aim of our work is to determinethe loss-of-function that might be associated to theconversion of AS from its monomeric functional state to its pathological oligomericby evaluating the impact of AS oligomerization on protein membrane-curvature sensitivity.We will present quantitative measurements on the interaction between monomericand oligomeric AS with vesicles varying in sizes using Fluorescence CorrelationSpectroscopy.