Abstract
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.
Keywords: Tryptophan, kynurenine, ischemia, stroke, neurodegeneration, depression, cognitive impairment, dementia.
Current Pharmaceutical Design
Title:The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia
Volume: 22 Issue: 8
Author(s): María Isabel Cuartero, Juan de la Parra, Alicia García-Culebras, Iván Ballesteros, Ignacio Lizasoain and María Ángeles Moro
Affiliation:
Keywords: Tryptophan, kynurenine, ischemia, stroke, neurodegeneration, depression, cognitive impairment, dementia.
Abstract: 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.
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Cite this article as:
Cuartero Isabel María, la Parra de Juan, García-Culebras Alicia, Ballesteros Iván, Lizasoain Ignacio and Moro Ángeles María, The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia, Current Pharmaceutical Design 2016; 22 (8) . https://dx.doi.org/10.2174/1381612822666151214125950
DOI https://dx.doi.org/10.2174/1381612822666151214125950 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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