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Assessing and Modulating Kynurenine Pathway Dynamics in Huntington’s Disease: Focus on Kynurenine 3-Monooxygenase

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Huntington’s Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

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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Authors and Affiliations

  1. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

    Korrapati V. Sathyasaikumar & Robert Schwarcz

  2. Department of Genetics and Genome Biology, University of Leicester, Leicester, UK

    Carlo Breda & Flaviano Giorgini

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  1. Korrapati V. Sathyasaikumar
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  2. Carlo Breda
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  3. Robert Schwarcz
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  4. Flaviano Giorgini
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Correspondence to Flaviano Giorgini .

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Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

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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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