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显而易见!TRIM蛋白在病毒和中枢神经系统疾病中的治疗潜力。

A No-Brainer! The Therapeutic Potential of TRIM Proteins in Viral and Central Nervous System Diseases.

作者信息

Hage Adam, Janes Mikhaila, Best Sonja M

机构信息

Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.

出版信息

Viruses. 2025 Apr 14;17(4):562. doi: 10.3390/v17040562.

DOI:10.3390/v17040562
PMID:40285004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12031127/
Abstract

Tripartite motif (TRIM) proteins comprise an important class of E3 ubiquitin ligases that regulate numerous biological processes including protein expression, cellular signaling pathways, and innate immunity. This ubiquitous participation in fundamental aspects of biology has made TRIM proteins a focus of study in many fields and has illuminated the negative impact they exert when functioning improperly. Disruption of TRIM function has been linked to the success of various pathogens and separately to the occurrence and development of several neurodegenerative diseases, making TRIM proteins an appealing candidate to study for novel therapeutic approaches. Here, we review the current findings on TRIM proteins that demonstrate their analogous properties in the distinct fields of viral infection and central nervous system (CNS) disorders. We also examine recent advancements in drug development and targeted protein degradation as potential strategies for TRIM-mediated therapeutic treatments and discuss the implications these technologies have on future research directions.

摘要

三聚体基序(TRIM)蛋白是一类重要的E3泛素连接酶,可调节多种生物学过程,包括蛋白质表达、细胞信号通路和先天免疫。TRIM蛋白在生物学基本方面的广泛参与使其成为许多领域的研究焦点,并揭示了其功能异常时所产生的负面影响。TRIM功能的破坏与各种病原体的成功感染以及几种神经退行性疾病的发生和发展有关,这使得TRIM蛋白成为研究新型治疗方法的有吸引力的候选对象。在这里,我们回顾了关于TRIM蛋白的当前研究结果,这些结果证明了它们在病毒感染和中枢神经系统(CNS)疾病这两个不同领域中的类似特性。我们还研究了药物开发和靶向蛋白质降解方面的最新进展,将其作为TRIM介导的治疗性治疗的潜在策略,并讨论了这些技术对未来研究方向的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34e/12031127/201bfef25886/viruses-17-00562-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34e/12031127/f771586464c0/viruses-17-00562-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34e/12031127/201bfef25886/viruses-17-00562-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34e/12031127/f771586464c0/viruses-17-00562-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d34e/12031127/201bfef25886/viruses-17-00562-g002.jpg

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本文引用的文献

1
LINC02282 promotes DNA methylation of TRIM6 by recruiting DNMTs to inhibit the progression of Parkinson's disease.LINC02282 通过招募DNA甲基转移酶促进TRIM6的DNA甲基化,从而抑制帕金森病的进展。
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Ubiquitin-A structural perspective.泛素——结构视角
Mol Cell. 2025 Jan 16;85(2):323-346. doi: 10.1016/j.molcel.2024.12.015.
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Targeted protein degradation with bifunctional molecules as a novel therapeutic modality for Alzheimer's disease & beyond.
以双功能分子进行靶向蛋白质降解作为治疗阿尔茨海默病及其他疾病的新型治疗方式。
Neurotherapeutics. 2025 Apr;22(3):e00499. doi: 10.1016/j.neurot.2024.e00499. Epub 2024 Dec 4.
4
TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication.TRIM7 泛素化 SARS-CoV-2 膜蛋白以限制细胞凋亡和病毒复制。
Nat Commun. 2024 Nov 30;15(1):10438. doi: 10.1038/s41467-024-54762-5.
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Targeted protein degradation: advances in drug discovery and clinical practice.靶向蛋白降解:药物发现和临床实践的进展。
Signal Transduct Target Ther. 2024 Nov 6;9(1):308. doi: 10.1038/s41392-024-02004-x.
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A Nanobody-based TRIM-away targets the intracellular protein degradation of African swine fever virus.基于纳米抗体的 TRIM-away 靶向非洲猪瘟病毒的细胞内蛋白降解。
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Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders.基于TRIM21的分子胶和PROTAC降解剂对多聚体蛋白的选择性降解
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Antibodies targeting the Crimean-Congo Hemorrhagic Fever Virus nucleoprotein protect via TRIM21.靶向克里米亚-刚果出血热病毒核蛋白的抗体通过 TRIM21 发挥保护作用。
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Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.利用模板化聚集物来降解致病的 tau 聚集体并改善运动功能。
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Aggregate-selective removal of pathological tau by clustering-activated degraders.聚集激活降解物对病理性 tau 的选择性清除。
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