title: Proteomic and oxidative stress analysis in human brain samples of Huntington disease.
abstract: Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG repeats in exon 1 of the huntingtin gene, affecting initially the striatum and progressively the cortex. This work reports a proteomic analysis of human brain postmortem samples obtained from striatum and cortex of patients with HD compared to samples of age- and sex-matched controls. Antioxidant defense proteins that were strongly induced in striatum, but also detectable in cortex, were identified as peroxiredoxins 1, 2, and 6, as well as glutathione peroxidases 1 and 6. The activities of other antioxidant enzymes such as mitochondrial superoxide dismutase and catalase were also increased in HD. Aconitase, a protein involved in energy metabolism, showed decreased activities in striatum of HD patients. Protein carbonyls, used as markers of oxidative stress, were increased in HD, and glial fibrillary acidic protein, aconitase, gamma-enolase, and creatine kinase B were identified as the main targets. Taken together, these results indicate that oxidative stress and damage to specific macromolecules would participate in the disease progression. Also, these data support the rationale for therapeutic strategies that either potentiate antioxidant defenses or avoid oxidative stress generation to delay disease progression.
authors.affiliation: Departament de Ciencies Mediques Basiques, IRBLLEIDA, Universitat de Lleida, 25008 Lleida, Spain.
authors.forename: Ma Alba
authors.initials: MA
authors.lastname: Sorolla
authors.forename: Gemma
authors.initials: G
authors.lastname: Reverter-Branchat
authors.forename: Jordi
authors.initials: J
authors.lastname: Tamarit
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Joaquim
authors.initials: J
authors.lastname: Ros
authors.forename: Elisa
authors.initials: E
authors.lastname: Cabiscol
mesh_terms: D015180:Electrophoresis, Gel, Two-Dimensional; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism; D050050:Protein Carbonylation; D040901:Proteomics; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase