Sorolla Ma Alba, Reverter-Branchat Gemma, Tamarit Jordi, Ferrer Isidre, Ros Joaquim, Cabiscol Elisa
Departament de Ciencies Mediques Basiques, IRBLLEIDA, Universitat de Lleida, 25008 Lleida, Spain.
Free Radic Biol Med. 2008 Sep 1;45(5):667-78. doi: 10.1016/j.freeradbiomed.2008.05.014. Epub 2008 May 28.
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.
亨廷顿舞蹈症（HD）是一种神经退行性疾病，由亨廷顿基因外显子1中CAG重复序列的扩增引起，最初影响纹状体，随后逐渐影响皮质。这项研究报告了对取自HD患者纹状体和皮质的人脑死后样本与年龄和性别匹配的对照样本进行的蛋白质组学分析。在纹状体中强烈诱导但在皮质中也可检测到的抗氧化防御蛋白被鉴定为过氧化物酶1、2和6，以及谷胱甘肽过氧化物酶1和6。HD患者中其他抗氧化酶如线粒体超氧化物歧化酶和过氧化氢酶的活性也有所增加。参与能量代谢的蛋白质乌头酸酶在HD患者的纹状体中活性降低。用作氧化应激标志物的蛋白质羰基在HD患者中增加，并且胶质纤维酸性蛋白、乌头酸酶、γ-烯醇化酶和肌酸激酶B被确定为主要靶点。综上所述，这些结果表明氧化应激和对特定大分子的损伤会参与疾病进展。此外，这些数据支持了通过增强抗氧化防御或避免氧化应激产生来延缓疾病进展的治疗策略的理论依据。
