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The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds. © 2013 Springer-Verlag Berlin Heidelberg.

Publication metadata

Author(s): Amaral M, Outeiro TF, Scrutton NS, Giorgini F

Publication type: Review

Publication status: Published

Journal: Journal of Molecular Medicine

Year: 2013

Volume: 91

Issue: 6

Pages: 705-713

Print publication date: 01/06/2013

Online publication date: 01/05/2013

ISSN (print): 0946-2716

ISSN (electronic): 1432-1440

URL: https://doi.org/10.1007/s00109-013-1046-9

DOI: 10.1007/s00109-013-1046-9

PubMed id: 23636512

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