Effect of amyloid oligomerization on the -synuclein curvature-dependent vesicle binding selectivity

GALLEA, JOSÉ IGNACIO; MAS, CARLOS; AMBROGGIO ERNESTO ESTEBAN; JAMES, NICOLAS; JAMESON, DAVID; CELEJ, MARÍA

Tucuman

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS) ? IX IberoAmerican Congress of Biophysics ? XLV Reunion Anual SAB 2016; 2016

Sociedad Argentina de Biofísica

Parkinson?s disease (PD) is a neurodegenerative movement disorder associatedwith axon degeneration of dopaminergic nigral neurons. Thecardinal pathological of PD, is the presence of proteinaceous highly organizedfibrillar inclusions, termed Lewy bodies, the main componentof which is the 140 aa protein -synuclein (AS). In addition, a numberof prefibrillar intermediates have been associated with PD pathology.These oligomers have been pointed as the most toxic species andthey are more likely located in axons and presynaptic terminals wherethey might damage synapses and dendrites. Functionally, AS assistsin the regulation of the distal reserve pool of synaptic vesicles whereprotein/membrane interactions would help to dock these vesicles in aregion distal from the synapsis. Among the several membrane propertiesthat modulate AS binding, curvature plays a key role. The aim ofour work is to determine the loss-of-function that might be associated tothe conversion of AS from its monomeric functional state to its pathologicaloligomeric form by evaluating the impact of AS oligomerizationon protein membrane-curvature sensitivity. We will present quantitativemeasurements on the interaction between monomeric and oligomericAS with vesicles varying in sizes using Fluorescence Correlation Spectroscopy.