Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
FASEB J. 2021 Apr;35(4):e21510. doi: 10.1096/fj.202002702R.
Neurological diseases are relatively complex diseases of a large system; however, the detailed mechanism of their pathogenesis has not been completely elucidated, and effective treatment methods are still lacking for some of the diseases. The SUMO (small ubiquitin-like modifier) modification is a dynamic and reversible process that is catalyzed by SUMO-specific E1, E2, and E3 ligases and reversed by a family of SENPs (SUMO/Sentrin-specific proteases). SUMOylation covalently conjugates numerous cellular proteins, and affects their cellular localization and biological activity in numerous cellular processes. A wide range of neuronal proteins have been identified as SUMO substrates, and the disruption of SUMOylation results in defects in synaptic plasticity, neuronal excitability, and neuronal stress responses. SUMOylation disorders cause many neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. By modulating the ion channel subunit, SUMOylation imbalance is responsible for the development of various channelopathies. The regulation of protein SUMOylation in neurons may provide a new strategy for the development of targeted therapeutic drugs for neurodegenerative diseases and channelopathies.
神经疾病是一个较大系统的相对复杂疾病；然而，其发病机制的详细机制尚未完全阐明，一些疾病仍然缺乏有效的治疗方法。SUMO（小泛素样修饰物）修饰是一种由 SUMO 特异性 E1、E2 和 E3 连接酶催化、并由一系列 SENPs（SUMO/Sentrin 特异性蛋白酶）逆转的动态可逆过程。SUMOylation 共价连接许多细胞蛋白，并影响它们在许多细胞过程中的细胞定位和生物活性。大量神经元蛋白已被鉴定为 SUMO 底物，SUMOylation 的破坏导致突触可塑性、神经元兴奋性和神经元应激反应缺陷。SUMOylation 障碍导致许多神经退行性疾病，如帕金森病、阿尔茨海默病和亨廷顿病。通过调节离子通道亚基，SUMOylation 失衡导致各种通道病的发生。神经元中蛋白质 SUMOylation 的调节可能为神经退行性疾病和通道病的靶向治疗药物的开发提供新策略。
