Bono-Yagüe José, Gómez-Escribano Ana Pilar, Millán José María, Vázquez-Manrique Rafael Pascual
Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Joint Unit for Rare Diseases IIS La Fe-CIPF, 46026 Valencia, Spain.
Antioxidants (Basel). 2020 Jul 2;9(7):577. doi: 10.3390/antiox9070577.
Huntington disease (HD) is a neurodegenerative condition and one of the so-called rare or minority diseases, due to its low prevalence (affecting 1-10 of every 100,000 people in western countries). The causative gene, , encodes huntingtin, a protein with a yet unknown function. Mutant huntingtin causes a range of phenotypes, including oxidative stress and the activation of microglia and astrocytes, which leads to chronic inflammation of the brain. Although substantial efforts have been made to find a cure for HD, there is currently no medical intervention able to stop or even delay progression of the disease. Among the many targets of therapeutic intervention, oxidative stress and inflammation have been extensively studied and some clinical trials have been promoted to target them. In the present work, we review the basic research on oxidative stress in HD and the strategies used to fight it. Many of the strategies to reduce the phenotypes associated with oxidative stress have produced positive results, yet no substantial functional recovery has been observed in animal models or patients with the disease. We discuss possible explanations for this and suggest potential ways to overcome it.
亨廷顿舞蹈症（HD）是一种神经退行性疾病，也是所谓的罕见病或小众疾病之一，因其发病率较低（在西方国家，每10万人中有1至10人患病）。致病基因 编码亨廷顿蛋白，该蛋白的功能尚不清楚。突变的亨廷顿蛋白会引发一系列表型，包括氧化应激以及小胶质细胞和星形胶质细胞的激活，进而导致脑部慢性炎症。尽管人们为治愈HD付出了巨大努力，但目前尚无能够阻止甚至延缓该疾病进展的医学干预措施。在众多治疗干预靶点中，氧化应激和炎症已得到广泛研究，并且已经开展了一些针对它们的临床试验。在本研究中，我们回顾了HD中氧化应激的基础研究以及对抗氧化应激所采用的策略。许多旨在减轻与氧化应激相关表型的策略已取得了积极成果，但在动物模型或该疾病患者中尚未观察到实质性的功能恢复。我们讨论了对此现象的可能解释，并提出了克服这一问题的潜在方法。
