The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia.
The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia.
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DOI：
10.2174/1381612822666151214125950
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发表时间：
2016
影响因子：
3.1
通讯作者：
Moro MÁ
中科院分区：
文献类型：
--
作者：
Cuartero MI;de la Parra J;García-Culebras A;Ballesteros I;Lizasoain I;Moro MÁ
犬尿氨酸是一种广泛的分解代谢物，通过“犬尿氨酸途径”（KP）从色氨酸中产生。除了它的外周作用，越来越多的证据表明KP在中枢神经系统（CNS）中的作用，介导生理和病理功能。事实上，这种途径的不平衡与一些神经退行性疾病，如阿尔茨海默氏症和亨廷顿氏病有关。KP分解代谢的改变在中风急性期和慢性期也有描述；然而，KP对急性缺血性损伤和脑卒中后慢性疾病（包括抑郁症和血管性痴呆）的病理生理的贡献，以及涉及脑卒中后KP调节的确切机制尚不清楚。更好地了解脑卒中后KP的调节和活性，可以为脑卒中急性期和慢性期提供新的药理工具。在这篇综述中，我们将概述由KP调制的中枢神经系统。我们将详细介绍KP在缺血性损伤中的作用，KP失衡如何引发脑卒中后认知功能的改变，以及开发新药的潜在靶点。
Kynurenines are a wide range of catabolites which derive from tryptophan through the “Kynurenine Pathway” (KP). In addition to its peripheral role, increasing evidence shows a role of the KP in the central nervous system (CNS), mediating both physiological and pathological functions. Indeed, an imbalance in this route has been associated with several neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. Altered KP catabolism has also been described during both acute and chronic phases of stroke; however the contribution of the KP to the pathophysiology of acute ischemic damage and of post-stroke disorders during the chronic phase including depression and vascular dementia, and the exact mechanisms implicated in the regulation of the KP after stroke are not well established yet. A better understanding of the regulation and activity of the KP after stroke could provide new pharmacological tools in both acute and chronic phases of stroke. In this review, we will make an overview of CNS modulation by the KP. We will detail the KP contribution in the ischemic damage, how the unbalance of the KP might trigger an alteration of the cognitive function after stroke as well as potential targets for the development of new drugs.