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犬尿氨酸与炎症:多发性硬化症治疗的一个重要轴。

Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment.

作者信息

Carrillo-Mora Paul, Landa-Solís Carlos, Valle-Garcia David, Luna-Angulo Alexandra, Avilés-Arnaut Hamlet, Robles-Bañuelos Benjamín, Sánchez-Chapul Laura, Rangel-López Edgar

机构信息

Clinical Neurosciences Division, National Institute of Rehabilitation "Luis Guillermo Ibarra Ibarra", Mexico City 14389, Mexico.

Tissue Engineering, Cell Therapy, and Regenerative Medicine Unit, National Institute of Rehabilitation "Luis Guillermo Ibarra Ibarra", Mexico City 14389, Mexico.

出版信息

Pharmaceuticals (Basel). 2024 Jul 25;17(8):983. doi: 10.3390/ph17080983.

DOI:10.3390/ph17080983
PMID:39204088
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11356993/
Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, there is a significant need to develop new therapeutic targets, especially for the progressive forms of the disease. This review article provides an overview of the most recent studies aimed at understanding the inflammatory processes that are activated in response to the accumulation of kynurenine pathway (KP) metabolites, which exacerbate an imbalance between immune system cells (e.g., Th1, Th2, and T reg) and promote the release of pro-inflammatory interleukins that modulate different mechanisms: membrane-receptors function; nuclear factors expression; and cellular signals. Together, these alterations trigger cell death mechanisms in brain cells and promote neuron loss and axon demyelination. This hypothesis could represent a remarkable approach for disease-modifying therapies for MS. Here, we also provide a perspective on the repositioning of some already approved drugs involved in other signaling pathways, which could represent new therapeutic strategies for MS treatment.

摘要

多发性硬化症(MS)是一种慢性炎症性自身免疫性神经疾病,其特征为脱髓鞘病变反复出现以及进行性残疾。目前,有多种疾病修正治疗方法,然而,迫切需要开发新的治疗靶点,尤其是针对该疾病的进展型。这篇综述文章概述了旨在了解因犬尿氨酸途径(KP)代谢产物积累而激活的炎症过程的最新研究,这些代谢产物会加剧免疫系统细胞(如Th1、Th2和调节性T细胞)之间的失衡,并促进促炎白细胞介素的释放,这些白细胞介素可调节不同机制:膜受体功能;核因子表达;以及细胞信号。这些改变共同触发脑细胞的细胞死亡机制,并促进神经元丢失和轴突脱髓鞘。这一假说可能代表了一种用于MS疾病修正治疗的显著方法。在此,我们还提供了关于重新定位一些已批准的参与其他信号通路的药物的观点,这些药物可能代表MS治疗的新策略。

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本文引用的文献

1
Kynurenine Metabolites in CSF and Plasma in Healthy Males.健康男性脑脊液和血浆中的犬尿氨酸代谢物
Int J Tryptophan Res. 2024 Apr 24;17:11786469241245323. doi: 10.1177/11786469241245323. eCollection 2024.
2
Kynurenine Pathway in Respiratory Diseases.呼吸系统疾病中的犬尿氨酸途径
Int J Tryptophan Res. 2024 Mar 14;17:11786469241232871. doi: 10.1177/11786469241232871. eCollection 2024.
3
Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment.多发性硬化症的综述:流行病学、病因、病理生理学和治疗。
网络药理学在中医药治疗神经退行性疾病中的应用
Planta Med. 2025 Apr;91(5):226-237. doi: 10.1055/a-2512-8928. Epub 2025 Jan 8.
Medicine (Baltimore). 2024 Feb 23;103(8):e37297. doi: 10.1097/MD.0000000000037297.
4
The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.褪黑素补充对多发性硬化症啮齿动物模型的神经行为结局和临床严重程度的影响:系统评价和荟萃分析。
Inflammopharmacology. 2024 Apr;32(2):927-944. doi: 10.1007/s10787-023-01414-7. Epub 2024 Jan 22.
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Resident immune responses to spinal cord injury: role of astrocytes and microglia.脊髓损伤的固有免疫反应:星形胶质细胞和小胶质细胞的作用
Neural Regen Res. 2024 Aug 1;19(8):1678-1685. doi: 10.4103/1673-5374.389630. Epub 2023 Dec 11.
6
On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging.色氨酸代谢产物 3-羟基邻氨基苯甲酸在秀丽隐杆线虫和小鼠衰老中的益处。
Nat Commun. 2023 Dec 14;14(1):8338. doi: 10.1038/s41467-023-43527-1.
7
Highly Effective Therapy Versus Escalation Approaches in Early Multiple Sclerosis: What Is the Future of Multiple Sclerosis Treatment?早期多发性硬化症的高效治疗与升级治疗方法:多发性硬化症治疗的未来是什么?
Neurol Clin. 2024 Feb;42(1):185-201. doi: 10.1016/j.ncl.2023.06.004. Epub 2023 Aug 21.
8
Crosstalk between Exercise-Derived Endocannabinoidome and Kynurenines: Potential Target Therapies for Obesity and Depression Symptoms.运动衍生内源性大麻素组与犬尿氨酸之间的相互作用:肥胖和抑郁症状的潜在靶向疗法
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Exp Mol Med. 2023 Jul;55(7):1371-1379. doi: 10.1038/s12276-023-01028-7. Epub 2023 Jul 3.