Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Neurochem Int. 2022 Sep;158:105363. doi: 10.1016/j.neuint.2022.105363. Epub 2022 Jun 3.
The kynurenine pathway receives increasing attention due to its involvement in central nervous system pathologies, i.a. neurodegenerative and psychiatric disorders, but also due to the contribution to the pathomechanism of neoplasms, including brain tumors. The present review focuses on kynurenine pathway activity in gliomas, brain tumors of glial origin. The upregulation of kynurenine pathway enzyme, indoleamine 2,3-dioxygenase (IDO), resulting in a decreased level of tryptophan and augmented kynurenine synthesis (increased (KYN/Trp ratio) are the most recognised hallmark of malignant transformation, characterised with immunomodulatory adaptations, providing an escape from defence mechanisms of the host, growth-beneficial milieu and resistance to some therapeutics. The review addresses, however, the oxidative/nitrosative stress-associated mechanisms of tryptophan catabolism, mainly the kynurenine pathway activity, linking them with glioma pathobiology.
由于色氨酸代谢途径（kynurenine pathway）与中枢神经系统疾病（如神经退行性疾病和精神疾病）有关，同时也与肿瘤（包括脑肿瘤）的发病机制有关，因此该途径受到了越来越多的关注。本综述主要聚焦于色氨酸代谢途径在神经胶质瘤（glioma），即神经胶质起源的脑肿瘤中的活性。该途径中酶（吲哚胺 2,3-双加氧酶，indoleamine 2,3-dioxygenase，IDO）的上调导致色氨酸水平降低和犬尿氨酸合成增加（KYN/Trp 比值升高），这是恶性转化的最显著特征，其特点是免疫调节适应，从而逃避宿主的防御机制、有利于生长的环境以及对某些治疗方法的耐药性。然而，本综述还探讨了与氧化/硝化应激相关的色氨酸代谢途径活性，主要是色氨酸代谢途径（kynurenine pathway），并将其与神经胶质瘤的病理生物学联系起来。
