Abstract：
Huntington\'s disease (HD) is a paradigm of a genetic neurodegenerative disorder characterized by the expansion of CAG repeats in the HTT gene. This extensive review investigates the molecular complexities of HD by highlighting the pathogenic mechanisms initiated by the mutant huntingtin protein. Adverse outcomes of HD include mitochondrial dysfunction, compromised protein clearance, and disruption of intracellular signaling, consequently contributing to the gradual deterioration of neurons. Numerous therapeutic strategies, particularly precision medicine, are currently used for HD management. Antisense oligonucleotides, such as Tominersen, play a leading role in targeting and modulating the expression of mutant huntingtin. Despite the promise of these therapies, challenges persist, particularly in improving delivery systems and the necessity for long-term safety assessments. Considering the future landscape, the review delineates promising directions for HD research and treatment. Innovations such as Clustered regularly interspaced short palindromic repeats associated system therapies (CRISPR)-based genome editing and emerging neuroprotective approaches present unprecedented opportunities for intervention. Collaborative interdisciplinary endeavors and a more insightful understanding of HD pathogenesis are on the verge of reshaping the therapeutic landscape. As we navigate the intricate landscape of HD, this review serves as a guide for unraveling the intricacies of this disease and progressing toward transformative treatments.
摘要：
亨廷顿氏病（HD）是遗传性神经退行性疾病的范例，其特征是HTT基因中CAG重复序列的扩展。这篇广泛的综述通过强调突变亨廷顿蛋白引发的致病机制来研究HD的分子复杂性。HD的不良结局包括线粒体功能障碍，受损的蛋白质清除率，和细胞内信号的破坏，从而导致神经元的逐渐恶化。许多治疗策略，特别是精准医学，目前用于HD管理。反义寡核苷酸,比如Tominersen,在靶向和调节突变型亨廷顿蛋白的表达中起主导作用。尽管这些疗法有希望，挑战依然存在,特别是在改善输送系统和长期安全评估的必要性。考虑到未来的景观，这篇综述描述了HD研究和治疗的有希望的方向。诸如聚集的定期间隔短回文重复相关系统疗法（CRISPR）的创新基于基因组编辑和新兴的神经保护方法为干预提供了前所未有的机会。跨学科的协作努力和对HD发病机制的更有见地的理解正处于重塑治疗前景的边缘。当我们驾驭复杂的高清景观时，这篇综述可以作为揭示这种疾病的复杂性并朝着转化治疗方向发展的指南。
