María Isabel Cuartero, Juan de la Parra, Alicia García-Culebras, Iván Ballesteros, Ignacio Lizasoain and María Ángeles Moro Pages 1060 - 1073 ( 14 )
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.
Tryptophan, kynurenine, ischemia, stroke, neurodegeneration, depression, cognitive impairment, dementia.
Unidad de Investigación Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Avenida Complutense s/n, 28040 Madrid, Spain.