双剑合璧:XJB-5-131 是亨廷顿氏病体细胞不稳定性和毒性的抑制因子

IF 2.1 Q3 NEUROSCIENCES Journal of Huntington's disease Pub Date : 2022-01-01 DOI:10.3233/JHD-210510
Pater Wipf, Aris A Polyzos, Cynthia T McMurray
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摘要

由于全球老年人口大幅增加,预计未来几年与年龄有关的疾病将急剧增多。其中,神经退行性疾病对患者及其家庭的情感和经济影响以及相关的医疗补贴费用将是最具破坏性的疾病之一。目前还没有治疗或挽救垂死脑细胞的方法。对这些疾病中的任何一种疾病采取可行的治疗方法都将是一项突破,并将为大量受影响的患者及其家庭带来福音。神经变性伴随着氧化损伤和炎症的加剧。虽然天然抗氧化剂在临床试验中大多以失败告终,但非天然的、以线粒体为靶点的亚硝基氧化物 XJB-5-131 的临床前表型研究预示着在高级动物模型或人体中进行进一步转化开发的良好前景。在此,我们将探讨合成抗氧化剂在治疗亨廷顿氏症方面的作用。XJB-5-131 的线粒体靶向特性前景广阔。它既是一种电子清除剂,又是一种抗氧化剂,通过相同的氧化还原机制同时减少体细胞扩张和毒性。通过淬灭活性氧,XJB-5-131 打破了疾病进展过程中氧化损伤上升与依赖氧化的 CAG 重复体生长之间的循环。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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A Double-Pronged Sword: XJB-5-131 Is a Suppressor of Somatic Instability and Toxicity in Huntington's Disease.

Due to large increases in the elderly populations across the world, age-related diseases are expected to expand dramatically in the coming years. Among these, neurodegenerative diseases will be among the most devastating in terms of their emotional and economic impact on patients, their families, and associated subsidized health costs. There is no currently available cure or rescue for dying brain cells. Viable therapeutics for any of these disorders would be a breakthrough and provide relief for the large number of affected patients and their families. Neurodegeneration is accompanied by elevated oxidative damage and inflammation. While natural antioxidants have largely failed in clinical trials, preclinical phenotyping of the unnatural, mitochondrial targeted nitroxide, XJB-5-131, bodes well for further translational development in advanced animal models or in humans. Here we consider the usefulness of synthetic antioxidants for the treatment of Huntington's disease. The mitochondrial targeting properties of XJB-5-131 have great promise. It is both an electron scavenger and an antioxidant, reducing both somatic expansion and toxicity simultaneously through the same redox mechanism. By quenching reactive oxygen species, XJB-5-131 breaks the cycle between the rise in oxidative damage during disease progression and the somatic growth of the CAG repeat which depends on oxidation.

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来源期刊
CiteScore
4.80
自引率
9.70%
发文量
60
期刊最新文献
Changes in 24(S)-Hydroxycholesterol Are Associated with Cognitive Performance in Early Huntington's Disease: Data from the TRACK and ENROLL HD Cohorts. Somatic CAG Repeat Stability in a Transgenic Sheep Model of Huntington's Disease. Mono- and Biallelic Inactivation of Huntingtin Gene in Patient-Specific Induced Pluripotent Stem Cells Reveal HTT Roles in Striatal Development and Neuronal Functions. Alterations in Cerebrospinal Fluid Urea Occur in Late Manifest Huntington's Disease. Characterizing Heart Rate Variability Response to Maximal Exercise Testing in People with Huntington's Disease.
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