The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominantly inherited progressive disorders, the clinical hallmark of which is loss of balance and coordination accompanied by slurred speech; onset is most often in adult life. Genetically, SCAs are grouped as repeat expansion SCAs, such as SCA3/Machado–Joseph disease (MJD), and rare SCAs that are caused by non-repeat mutations, such as SCA5. Most SCA mutations cause prominent damage to cerebellar Purkinje neurons with consecutive cerebellar atrophy, although Purkinje neurons are only mildly affected in some SCAs. Furthermore, other parts of the nervous system, such as the spinal cord, basal ganglia and pontine nuclei in the brainstem, can be involved. As there is currently no treatment to slow or halt SCAs (many SCAs lead to premature death), the clinical care of patients with SCA focuses on managing the symptoms through physiotherapy, occupational therapy and speech therapy. Intense research has greatly expanded our understanding of the pathobiology of many SCAs, revealing that they occur via interrelated mechanisms (including proteotoxicity, RNA toxicity and ion channel dysfunction), and has led to the identification of new targets for treatment development. However, the development of effective therapies is hampered by the heterogeneity of the SCAs; specific therapeutic approaches may be required for each disease.

脊髓小脑共济失调（SCA）是常染色体显性遗传性进行性疾病的遗传异质性组，其临床标志是失去平衡和协调性并伴有口齿不清。发病最常见于成年生活。从遗传学上讲，SCA分为重复扩增SCA，例如SCA3 /马查多–约瑟夫病（MJD），以及由非重复突变引起的稀有SCA，例如SCA5。大多数SCA突变会导致小脑浦肯野神经元出现连续性小脑萎缩，但浦肯野神经元仅在某些SCA中受到轻度影响。此外，可能涉及神经系统的其他部分，例如脑干中的脊髓，基底神经节和桥脑核。由于目前尚无用于减缓或停止SCA的治疗方法（许多SCA会导致过早死亡），SCA患者的临床护理重点在于通过物理疗法，职业疗法和言语疗法来控制症状。深入的研究极大地扩展了我们对许多SCA病理生物学的理解，揭示了它们是通过相互关联的机制（包括蛋白毒性，RNA毒性和离子通道功能障碍）发生的，并导致了新靶点的发现，从而确定了治疗发展的新靶点。但是，SCA的异质性阻碍了有效疗法的发展。每种疾病可能需要特定的治疗方法。揭示了它们是通过相互关联的机制（包括蛋白毒性，RNA毒性和离子通道功能障碍）发生的，并导致了新的治疗方法靶标的确定。但是，SCA的异质性阻碍了有效疗法的发展。每种疾病可能需要特定的治疗方法。揭示了它们是通过相互关联的机制（包括蛋白毒性，RNA毒性和离子通道功能障碍）发生的，并导致了新的治疗方法靶标的确定。但是，SCA的异质性阻碍了有效疗法的发展。每种疾病可能需要特定的治疗方法。