SELECTIVE OXIDATION OF ALPHA-SYNUCLEIN ON MEMBRANE INTERPHASE

GIMENEZ E; BORSARELLI CD; JOVIN TM; CORSICO B; FALOMIR LOCKHART LJ

Mar del Plata

Congreso; XXX Reunión Anual de la SAN 2015; 2015

Sociedad Argentina de Investigación en Neurociencias

Parkinson´s disease is a progressive neurodegenerative disorder, histologically defined by intracellular aggregates of proteins, α-Synuclein (aSyn) mainly, and lipids. Aggregation of aSyn has been associated with selective loss of dopaminergic neurons, in combination with external factors related to lipid and protein oxidation and mitochondrial malfunction. Early intermediates of aSyn aggregates are thought to be the main culprits, rather than mature amyloid fibrils. But a comprehensive description of the relationship between protein aggregation and neuronal death is still missing. We decided to evaluate the effects of aSyn oxidation and formation of crosslinked oligómeros comparing aSyn free form and the one associated to phospholipid membranes. aSyn diTyr crosslink was selectively formed using Ru(II) photo-sensitizers in the presence and absence of phospholipid membranes in order to study aSyn´s conformational changes and the role of lipids during oxidative stress modifications of aSyn. The presence of diTyrosine crosslinks was demostrated by fluorescence and westernblot.