Oxidation and nitration of α-synuclein and their implications in neurodegenerative diseases

Synucleinopathies include Parkinson's disease, dementia with Lewy bodies, Lewy body variant of Alzheimer's disease and multiple system atrophy, among the most relevant diseases. All of these diseases are characterized by the presence of amyloid inclusions in neurons, which are rich in the aggregate alpha-synuclein protein. What is the biological mechanism concerned in the gain-of-function that implicates the participation of alpha-synuclein in these diseases? Post-translational modifications of alpha-synuclein induced by nitroxidative stress are a relevant hypothesis that may explain many of the experimental data. We will review the biophysical and biochemical properties of alpha-synuclein, methionine residues oxidation, nitration and oxidation of tyrosine residues in alpha-synuclein, and modifications of alpha-synuclein mediated by proteins and lipids under nitroxidative stress conditions. The biological consequences of these modifications are analyzed in terms of the properties of alpha-synuclein oligomerization and fibrillation, degradation of alpha-synuclein and the implications in the immunological response. (C) 2013 Elsevier Inc. All rights reserved.