Abstract
The link between disturbances in kynurenine pathway (KP) metabolism and Huntington’s disease (HD) pathogenesis has been explored for a number of years. Several novel genetic and pharmacological tools have recently been developed to modulate key regulatory steps in the KP such as the reaction catalyzed by the enzyme kynurenine 3-monooxygenase (KMO). This insight has offered new options for exploring the mechanistic link between this metabolic pathway and HD, and provided novel opportunities for the development of candidate drug-like compounds. Here, we present an overview of the field, focusing on some novel approaches for interrogating the pathway experimentally.
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Acknowledgements
We are grateful to Louis Fernandes (Harvard Brain Tissue Resource Center, Boston, MA, USA) for providing human brain tissue for this study. We also thank Erin Stachowski for excellent technical assistance with the measurement of 3-HK levels and KP enzyme activities in human brain tissues. F.G. thanks the Medical Research Council for funding (MR/N00373X/1).
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Sathyasaikumar, K.V., Breda, C., Schwarcz, R., Giorgini, F. (2018). Assessing and Modulating Kynurenine Pathway Dynamics in Huntington’s Disease: Focus on Kynurenine 3-Monooxygenase. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_18
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