Wan Linlin, Xu Keqin, Chen Zhao, Tang Beisha, Jiang Hong
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, China.
Front Cell Neurosci. 2018 Sep 19;12:290. doi: 10.3389/fncel.2018.00290. eCollection 2018.
Post-translational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, SUMOylation, etc., of proteins can modulate protein properties such as intracellular distribution, activity, stability, aggregation, and interactions. Therefore, PTMs are vital regulatory mechanisms for multiple cellular processes. Spinocerebellar ataxias (SCAs) are hereditary, heterogeneous, neurodegenerative diseases for which the primary manifestation involves ataxia. Because the pathogenesis of most SCAs is correlated with mutant proteins directly or indirectly, the PTMs of disease-related proteins might functionally affect SCA development and represent potential therapeutic interventions. Here, we review multiple PTMs related to disease-causing proteins in SCAs pathogenesis and their effects. Furthermore, we discuss these PTMs as potential targets for treating SCAs and describe translational therapies targeting PTMs that have been published.
蛋白质的翻译后修饰（PTM），包括磷酸化、乙酰化、泛素化、小泛素样修饰等，能够调节蛋白质的特性，如细胞内分布、活性、稳定性、聚集和相互作用。因此，PTM是多种细胞过程的重要调控机制。脊髓小脑共济失调（SCA）是一类遗传性、异质性神经退行性疾病，主要表现为共济失调。由于大多数SCA的发病机制直接或间接与突变蛋白相关，疾病相关蛋白的PTM可能在功能上影响SCA的发展，并代表潜在的治疗干预措施。在此，我们综述了与SCA发病机制中致病蛋白相关的多种PTM及其作用。此外，我们讨论了这些PTM作为治疗SCA的潜在靶点，并描述了已发表的针对PTM的转化疗法。
