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犬尿氨酸作为治疗炎症性疾病的新靶点。

Kynurenines as a Novel Target for the Treatment of Inflammatory Disorders.

机构信息

Department of Pharmacodynamics, Medical University of Bialystok, A. Mickiewicza 2C, 15-222 Bialystok, Poland.

Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.

出版信息

Cells. 2024 Jul 26;13(15):1259. doi: 10.3390/cells13151259.

Abstract

This review discusses the potential of targeting the kynurenine pathway (KP) in the treatment of inflammatory diseases. The KP, responsible for the catabolism of the amino acid tryptophan (TRP), produces metabolites that regulate various physiological processes, including inflammation, cell cycle, and neurotransmission. These metabolites, although necessary to maintain immune balance, may accumulate excessively during inflammation, leading to systemic disorders. Key KP enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), tryptophan 2,3-dioxygenase (TDO), and kynurenine 3-monooxygenase (KMO) have been considered promising therapeutic targets. It was highlighted that both inhibition and activation of these enzymes may be beneficial, depending on the specific inflammatory disorder. Several inflammatory conditions, including autoimmune diseases, for which modulation of KP activity holds therapeutic promise, have been described in detail. Preclinical studies suggest that this modulation may be an effective treatment strategy for diseases for which treatment options are currently limited. Taken together, this review highlights the importance of further research on the clinical application of KP enzyme modulation in the development of new therapeutic strategies for inflammatory diseases.

摘要

这篇综述讨论了靶向色氨酸代谢途径(KP)治疗炎症性疾病的潜力。KP 负责分解氨基酸色氨酸(TRP),产生调节各种生理过程的代谢物,包括炎症、细胞周期和神经传递。这些代谢物虽然对维持免疫平衡是必要的,但在炎症期间可能会过度积累,导致全身紊乱。关键的 KP 酶,如吲哚胺 2,3-双加氧酶 1(IDO1)、吲哚胺 2,3-双加氧酶 2(IDO2)、色氨酸 2,3-双加氧酶(TDO)和犬尿氨酸 3-单加氧酶(KMO),已被认为是有前途的治疗靶点。研究表明,这些酶的抑制和激活可能都有治疗益处,具体取决于特定的炎症性疾病。本文详细描述了几种炎症性疾病,包括自身免疫性疾病,KP 活性的调节对这些疾病具有治疗潜力。临床前研究表明,这种调节可能是目前治疗选择有限的疾病的一种有效治疗策略。总之,这篇综述强调了进一步研究 KP 酶调节在炎症性疾病新治疗策略开发中的临床应用的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cacc/11311768/d0ad611d7b3d/cells-13-01259-g001.jpg

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