Quinolinate-induced cortical cholinergic damage: modulation by tryptophan metabolites

Jhamandas, Khem; Boegman, R.J.; Beninger, Richard J.; Bialik, Martin

doi:10.1016/0006-8993(90)90826-w

Cited by 69 publications

(58 citation statements)

References 16 publications

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“…We previously showed that PIC is also produced by human fetal astrocytes (Guillemin et al, 2001). PIC is an endogenous neuroprotective compound within the brain (Jhamandas et al, 1990). In nanomolar concentrations, it protects against QUIN-and kainic acid-induced neurotoxicity (Vrooman et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Kynurenine Pathway in Human Neurons

et al. 2007

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The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the kynurenine pathway in human neurons and the human SK-N-SH neuroblastoma cell line and found that the kynurenine pathway enzymes were variably expressed. Picolinic carboxylase was expressed only in primary and some adult neurons but not in SK-N-SH cells. Because of this difference, SK-N-SH cells were able to produce the excitotoxin quinolinic acid, whereas human neurons produced the neuroprotectant picolinic acid. The net result of kynurenine pathway induction in human neurons is therefore predicted to result in neuroprotection, immune regulation, and tumor inhibition, whereas in SK-N-SH cells, it may result in neurotoxicity, immune tolerance, and tumor promotion. This study represents the first comprehensive characterization of the kynurenine pathway in neurons and the first description of the involvement of the kynurenine pathway as a mechanism for controlling both tumor cell neurotoxicity and persistence.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Kynurenine Pathway in Human Neurons

et al. 2007

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“…According to some early studies, the proposed deleterious effects of 3-OH-L-KYN, a metabolite produced by kynurenine 3-monooxygenase (KMO), are mediated by free radicals and not glutamate receptors, and some of its detrimental actions may be due to its metabolite, 3-OH-ANA, via its auto-oxidation, leading to the production of superoxide anion [218][219][220][221].…”

Section: -Hydroxy-l-kynurenine and 3-hydroxyanthranilic Acidmentioning

confidence: 99%

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

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Szalárdy

et al. 2018

JAD

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The pathomechanism of Alzheimer's disease (AD) certainly involves mitochondrial disturbances, glutamate excitotoxicity, and neuroinflammation. The three main aspects of mitochondrial dysfunction in AD, i.e., the defects in dynamics, altered bioenergetics, and the deficient transport act synergistically. In addition, glutamatergic neurotransmission is affected in several ways. The balance between synaptic and extrasynaptic glutamatergic transmission is shifted toward the extrasynaptic site contributing to glutamate excitotoxicity, a phenomenon augmented by increased glutamate release and decreased glutamate uptake. quinolinic acid, has been demonstrated to be neurotoxic, promoting glutamate excitotoxicity, reactive oxygen species production, lipid peroxidation, and microglial neuroinflammation, and its abundant presence in AD pathologies has been demonstrated. Finally, the neuroprotective metabolite, kynurenic acid, has been associated with antagonistic effects at glutamate receptors, free radical scavenging, and immunomodulation, giving rise to potential therapeutic implications. This review presents the multiple connections of KYN pathwayrelated alterations to three main domains of AD pathomechanism, such as mitochondrial dysfunction, excitotoxicity, and neuroinflammation, implicating possible therapeutic options.3

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“…QUIN is increased in the cerebrospinal fluid (CSF) of human subjects following inflammatory brain injury (8,9) and it has been proposed that QUIN contributes to the neuroexcitatory signs and pathology associated with cerebral malaria (10,11). The neurotoxic and neuroexcitatory actions of QUIN are mediated at receptors sensitive to N-methyl-D-aspartate (NMDA) (3,4,(12)(13)(14). Picolinic acid (PIC), on the other hand, has been reported to inhibit neurotoxic activity induced by QUIN treatment (15)(16)(17).…”

mentioning

confidence: 99%