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Role of neddylation in neurological development and diseases
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2021-01-19 , DOI: 10.1002/bab.2112
Xin He 1 , Ainong Zhu 2 , Jianguo Feng 3, 4 , Xiaobin Wang 3
Affiliation  

Neddylation, a posttranslational protein modification, refers to the specific conjugation of NEDD8 to substrates, which is of great significance to various biological processes. Besides members of the cullin protein family, other key proteins can act as a substrate for neddylation modification, which remarkably influences neurodevelopment and neurodegenerative diseases. Normal levels of protein neddylation contribute to nerve growth, synapse strength, neurotransmission, and synaptic plasticity, whereas overactivation of protein neddylation pathways lead to apoptosis, autophagy of neurons, and tumorigenesis. Furthermore, impaired neddylation causes neurodegenerative diseases. These facts suggest that neddylation may be a target for treatment of these diseases. This review focuses on the current understanding of neddylation function in neurodevelopment as well as neurodegenerative diseases. Meanwhile, the recent view that different level of neddylation pathway may contribute to the opposing disease progression, such as neoplasms and Alzheimer's disease, is discussed. The review also discusses neddylation inhibitors, which are currently being tested in clinical trials. However, potential drawbacks of these drugs are noted, which may benefit the development of new pharmaceutical strategies in the treatment of nervous system diseases.

中文翻译:

neddylation 在神经发育和疾病中的作用

Neddylation是一种翻译后蛋白质修饰,是指NEDD8与底物的特异性结合,对各种生物学过程具有重要意义。除了 cullin 蛋白家族的成员,其他关键蛋白可以作为 neddylation 修饰的底物,显着影响神经发育和神经退行性疾病。正常水平的蛋白质 neddylation 有助于神经生长、突触强度、神经传递和突触可塑性,而蛋白质 neddylation 途径的过度激活会导致细胞凋亡、神经元自噬和肿瘤发生。此外,neddylation 受损会导致神经退行性疾病。这些事实表明,neddylation 可能是治疗这些疾病的目标。本综述侧重于当前对神经发育和神经退行性疾病中的 neddylation 功能的理解。同时,讨论了最近的观点,即不同水平的neddylation途径可能有助于相反的疾病进展,例如肿瘤和阿尔茨海默病。该评论还讨论了 neddylation 抑制剂,目前正在临床试验中进行测试。然而,注意到这些药物的潜在缺点,这可能有利于开发治疗神经系统疾病的新药物策略。该评论还讨论了 neddylation 抑制剂,目前正在临床试验中进行测试。然而,注意到这些药物的潜在缺点,这可能有利于开发治疗神经系统疾病的新药物策略。该评论还讨论了 neddylation 抑制剂,目前正在临床试验中进行测试。然而,注意到这些药物的潜在缺点,这可能有利于开发治疗神经系统疾病的新药物策略。
更新日期:2021-01-19
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