title: Oxidation and nitration of α-synuclein and their implications in neurodegenerative diseases.
abstract: 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 α-synuclein protein. What is the biological mechanism concerned in the gain-of-function that implicates the participation of α-synuclein in these diseases? Post-translational modifications of α-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 α-synuclein, methionine residues oxidation, nitration and oxidation of tyrosine residues in α-synuclein, and modifications of α-synuclein mediated by proteins and lipids under nitroxidative stress conditions. The biological consequences of these modifications are analyzed in terms of the properties of α-synuclein oligomerization and fibrillation, degradation of α-synuclein and the implications in the immunological response.
authors: Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Av. Gral. Flores 2125, 11800 Montevideo, Uruguay.
authors: Cecilia
authors: C
authors: Chavarría
authors: José M
authors: JM
authors: Souza
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009574:Nitro Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009574:Nitro Compounds; D051844:alpha-Synuclein