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.
Keywords:
Huntington’s disease; Kynurenine 3-monooxygenase (KMO); Kynurenine pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Animals
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Brain / drug effects
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Brain / metabolism
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Brain / pathology*
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Disease Models, Animal
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Female
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Humans
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Huntingtin Protein / genetics
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Huntingtin Protein / metabolism
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Huntington Disease / drug therapy
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Huntington Disease / genetics
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Huntington Disease / pathology*
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Kynurenine / metabolism*
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Kynurenine 3-Monooxygenase / antagonists & inhibitors
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Kynurenine 3-Monooxygenase / metabolism*
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Male
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Metabolic Networks and Pathways / drug effects*
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Metabolic Networks and Pathways / genetics
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Middle Aged
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use
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Tryptophan / metabolism
Substances
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Enzyme Inhibitors
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HTT protein, human
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Huntingtin Protein
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Neuroprotective Agents
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Kynurenine
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Tryptophan
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Kynurenine 3-Monooxygenase