RNA结合蛋白:在神经毒性中的作用?

IF 2.9 3区 医学 Q2 NEUROSCIENCES Neurotoxicity Research Pub Date : 2023-12-01 Epub Date: 2023-09-30 DOI:10.1007/s12640-023-00669-w
Andrea Ocharán-Mercado, Jaqueline Loaeza-Loaeza, Yaneth Castro-Coronel, Leonor C Acosta-Saavedra, Luisa C Hernández-Kelly, Daniel Hernández-Sotelo, Arturo Ortega
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引用次数: 0

摘要

尽管在治疗神经退行性疾病方面做出了持续的努力,但在分子水平上,人们对了解和产生治疗这些恶性肿瘤的新方法知之甚少。因此,神经源性疾病是老年人死亡的主要原因也就不足为奇了。神经元需要复杂的细胞机制来维持适当的蛋白质稳态。这些细胞通常对转录后水平的基因表达控制的丧失敏感。翻译后控制对可通过RNA结合蛋白调节的细胞内过程或环境因素产生的信号作出反应。这些蛋白质通过一个或多个RNA结合结构域识别RNA,并形成核糖核蛋白,该蛋白主要参与转录后过程的调节,从剪接到翻译机制的结合调节,从而相对快速和精确地调节转录组。神经毒性是对中枢神经系统的结构和功能产生不利影响的药物的生物、化学或物理相互作用的结果。神经元和神经胶质细胞中RBPs的适当水平或功能的破坏会引发神经毒性事件,这些事件与神经退行性疾病有关,如脊髓性肌萎缩(SMA)、肌萎缩性侧索硬化症(ALS)、脆性X综合征(FXS)和额颞叶痴呆(FTD)等。RBPs与神经退行性疾病之间的联系为干预这些神经退行性病变的潜在新治疗靶点开辟了新的前景。在这篇文章中,总结了RBPs在神经退行性疾病RNA加工中可能发挥作用的分子机制的最新发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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RNA-Binding Proteins: A Role in Neurotoxicity?

Despite sustained efforts to treat neurodegenerative diseases, little is known at the molecular level to understand and generate novel therapeutic approaches for these malignancies. Therefore, it is not surprising that neurogenerative diseases are among the leading causes of death in the aged population. Neurons require sophisticated cellular mechanisms to maintain proper protein homeostasis. These cells are generally sensitive to loss of gene expression control at the post-transcriptional level. Post-translational control responds to signals that can arise from intracellular processes or environmental factors that can be regulated through RNA-binding proteins. These proteins recognize RNA through one or more RNA-binding domains and form ribonucleoproteins that are critically involved in the regulation of post-transcriptional processes from splicing to the regulation of association of the translation machinery allowing a relatively rapid and precise modulation of the transcriptome. Neurotoxicity is the result of the biological, chemical, or physical interaction of agents with an adverse effect on the structure and function of the central nervous system. The disruption of the proper levels or function of RBPs in neurons and glial cells triggers neurotoxic events that are linked to neurodegenerative diseases such as spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), fragile X syndrome (FXS), and frontotemporal dementia (FTD) among many others. The connection between RBPs and neurodegenerative diseases opens a new landscape for potentially novel therapeutic targets for the intervention of these neurodegenerative pathologies. In this contribution, a summary of the recent findings of the molecular mechanisms involved in the plausible role of RBPs in RNA processing in neurodegenerative disease is discussed.

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来源期刊
Neurotoxicity Research
Neurotoxicity Research 医学-神经科学
CiteScore
7.70
自引率
5.40%
发文量
164
审稿时长
6-12 weeks
期刊介绍: Neurotoxicity Research is an international, interdisciplinary broad-based journal for reporting both basic and clinical research on classical neurotoxicity effects and mechanisms associated with neurodegeneration, necrosis, neuronal apoptosis, nerve regeneration, neurotrophin mechanisms, and topics related to these themes. Published papers have focused on: NEURODEGENERATION and INJURY Neuropathologies Neuronal apoptosis Neuronal necrosis Neural death processes (anatomical, histochemical, neurochemical) Neurodegenerative Disorders Neural Effects of Substances of Abuse NERVE REGENERATION and RESPONSES TO INJURY Neural Adaptations Neurotrophin mechanisms and actions NEURO(CYTO)TOXICITY PROCESSES and NEUROPROTECTION Excitatory amino acids Neurotoxins, endogenous and synthetic Reactive oxygen (nitrogen) species Neuroprotection by endogenous and exogenous agents Papers on related themes are welcome.
期刊最新文献
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