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Property "Has-20abstract" (as page type) with input value "Upregulation-20of-20the-20kynurenine-20pathway-20(KP)-20of-20tryptophan-20metabolism-20is-20commonly-20observed-20in-20neurodegenerative-20disease.-20When-20activated,-20L-2Dkynurenine-20(KYN)-20increases-20in-20the-20periphery-20and-20central-20nervous-20system-20where-20it-20is-20further-20metabolised-20to-20other-20neuroactive-20metabolites-20including-203-2Dhydroxykynurenine-20(3-2DHK),-20kynurenic-20acid-20(KYNA)-20and-20quinolinic-20acid-20(QUIN).-20Particularly-20biologically-20relevant-20metabolites-20are-203-2DHK-20and-20QUIN,-20formed-20downstream-20of-20the-20enzyme-20kynurenine-203-2Dmonooxygenase-20(KMO)-20which-20plays-20a-20pivotal-20role-20in-20maintaining-20KP-20homeostasis.-20Indeed,-20excessive-20production-20of-203-2DHK-20and-20QUIN-20has-20been-20described-20in-20neurodegenerative-20disease-20including-20Alzheimer's-20disease-20and-20Huntington's-20disease.-20In-20this-20study,-20we-20characterise-20KMO-20activity-20in-20human-20primary-20neurons-20and-20identified-20new-20mechanisms-20by-20which-20KMO-20activation-20mediates-20neurotoxicity.-20We-20show-20that-20while-20transient-20activation-20of-20the-20KP-20promotes-20synthesis-20of-20the-20essential-20co-2Denzyme-20nicotinamide-20adenine-20dinucleotide-20(NAD-3Csup-3E+-3C-2Fsup-3E),-20allowing-20cells-20to-20meet-20short-2Dterm-20increased-20energy-20demands,-20chronic-20KMO-20activation-20induces-20production-20of-20reactive-20oxygen-20species-20(ROS),-20mitochondrial-20damage-20and-20decreases-20spare-2Drespiratory-20capacity-20(SRC).-20We-20further-20found-20that-20these-20events-20generate-20a-20vicious-2Dcycle,-20as-20mitochondrial-20dysfunction-20further-20shunts-20the-20KP-20towards-20the-20KMO-20branch-20of-20the-20KP-20to-20presumably-20enhance-20QUIN-20production.-20These-20mechanisms-20may-20be-20especially-20relevant-20in-20neurodegenerative-20disease-20as-20neurons-20are-20highly-20sensitive-20to-20oxidative-20stress-20and-20mitochondrial-20impairment." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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