2026 年第 4 期 第 21 卷

线粒体功能障碍在脊髓小脑性共济失调3型中的作用机制研究进展

Research progress on the mechanism of mitochondrial dysfunction in spinocerebellar ataxia type 3

作者：刘艺璇蒲娟娟唐秘博

英文作者：Liu Yixuan Pu Juanjuan Tang Mibo

单位：郑州大学第一附属医院老年医学科，郑州450000

英文单位：Department of Geriatrics the First Affiliated Hospital of Zhengzhou University Zhengzhou 450000 China

关键词：脊髓小脑性共济失调3型；线粒体功能障碍；作用机制；三磷酸腺苷；氧化应激

英文关键词：Spinocerebellarataxiatype3;Mitochondrialdysfunction;Mechanism;Adenosinetriphosphate;Oxidativestress

• 摘要：

• 脊髓小脑性共济失调3型（SCA3）是常染色体显性遗传神经退行性疾病，是最常见的神经遗传变性疾病之一。致病核心为ATXN3基因CAG重复序列异常扩增致突变型 ataxin-3 蛋白积累，发病机制尚未完全阐明，且无有效治疗药物。线粒体功能障碍是其关键病理机制。本文围绕线粒体功能障碍在SCA3中的作用展开。SCA3中线粒体功能障碍表现为膜电位降低、活性氧升高及三磷酸腺苷生成减少等生物能量学缺陷。其机制涉及突变ataxin-3通过影响电压依赖性阴离子通道1去泛素化干扰线粒体自噬，氧化应激与线粒体损伤形成恶性循环，线粒体质量控制失衡，以及凋亡途径存在组织特异性易感性。深入研究这些机制对开发治疗策略具有重要意义，未来针对线粒体保护与代谢调节的多维度靶点研究，可为SCA3治疗提供新的转化方向。本文对线粒体功能障碍在SCA3中的作用及其机制的研究进展进行综述。

• Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disease and one of the most common neurogenetic degenerative disorders. The core pathogenic factor is the abnormal expansion of CAG trinucleotide repeat sequences in the ATXN3 gene, which leads to the accumulation of mutant ataxin-3 protein. Its pathogenesis has not been fully elucidated, and there is no effective therapeutic drug available. Mitochondrial dysfunction is a key pathological mechanism of SCA3. This article focuses on the role of mitochondrial dysfunction in SCA3. Mitochondrial dysfunction in SCA3 is characterized by bioenergetic defects such as decreased membrane potential, elevated reactive oxygen species and reduced adenosine triphosphate production. The underlying mechanisms involve the interference of mutant ataxin-3 with mitophagy by affecting the deubiquitination of voltage-dependent anion channel 1, a vicious cycle formed by oxidative stress and mitochondrial damage, imbalance of mitochondrial quality control, and tissue-specific susceptibility of apoptotic pathways. In-depth study of these mechanisms is of great significance for the development of therapeutic strategies. Future multi-dimensional target research focusing on mitochondrial protection and metabolic regulation may provide new translational directions for the treatment of SCA3. This article reviews the research progress on the role and underlying mechanisms of mitochondrial dysfunction in SCA3.