“Oxidative modification of alpha-synuclein modifies its cytotoxicity”

LISANDROJ.FALOMIR LOCKHART; C.D.BORSARELLI; V.OSTATNÁ; JONATHAN A. FAUERBACH; PALECEK E.; E.A. JARES-ERIJMAN; T.M. JOVIN

SAN DIEGO, CALIFORNIA

Conferencia; Annual Meeting #55 of the Biophysical Society; 2012

Parkinson’s Disease (PD) is a progressive neurodegenerative condition present in more than 1% of the population older than 60 years. The clinical picture is characterized by motor symptoms, memory loss, reduction or loss of sense of smell and sleep disorders that mostly arise after selective loss of dopaminergic neurons. Synucleopathies, like PD, are histologically defined by amyloid aggregates of proteins and lipids, known as Lewy Bodies, of which a-Synuclein (aSyn) is the most abundant components. Nevertheless a comprehensive description that explains the relationship between the amyloid aggregates and the selective cell death is still to be achieved, specially because the cellular toxic species have not yet been identified. New data point towards the early aggregates (oligomers) rather to the final fibrillar amyloid structures as the main “culprits”. Different genetic alterations have been correlated to the higher expression levels and the aggregation of aSyn. Nevertheless, the factors that triggers this procedure are mostly not understood. An underplaying oxidative process, linked also to mitochondrial functionality (Figure 1), seems to be undoubtedly involved. The functions of aSyn are still unknown, but it is supposed to have the capacity to adopt multiple spatial configurations in order to sense the presence of different interacting partners that could stabilize (or disrupt) its normal functions, as well as due to oxidative modifications.