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Notes:
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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, γ-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.
This work has been supported by Grants BFU2004-00593/BMC, BFU2007-66249, and CSD2007-20 Consolider Ingenio 2010 from the Ministerio de Educación y Ciencia (Spain) and SGR2005-00677 from the Generalitat de Catalunya. M. A. Sorolla is the recipient of a Ph.D. fellowship from the Ministerio de Educación y Ciencia (Spain) |
