Quinolinic Acid and Active Oxygens

Goda, Katalin; Kishimoto, Ritsuko; Shimizu, Soichi; Hamane, Y.; Ueda, Makoto

doi:10.1007/978-1-4613-0381-7_38

Cited by 54 publications

(7 citation statements)

References 11 publications

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“…Another main mechanism of QA neurotoxicity is via lipid peroxidation [ 166 ]. Few studies have suggested that QA forms a complex with iron (Fe), and electron transfer from this complex to oxygen causes the formation of reactive oxygen species (ROS) which then carries out lipid peroxidation [ 167 , 168 ]. QA-Fe(II) complexes display significant pro-oxidant characteristics that could have implications for QA neurotoxicity [ 169 ].…”

Section: Toxin-induced Experimental Models Of Memory Impairmentmentioning

confidence: 99%

Toxin-Induced Experimental Models of Learning and Memory Impairment

Kumar

Cho

et al. 2016

IJMS

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Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson’s disease dementia and Alzheimer’s disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

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Section: Toxin-induced Experimental Models Of Memory Impairmentmentioning

confidence: 99%

Toxin-Induced Experimental Models of Learning and Memory Impairment

Kumar

Cho

et al. 2016

IJMS

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“…High levels of QA result in hyperactivation of this receptor and excitotoxicity, as well as glutamate toxicity due to excessive glutamate release from astrocytes and inhibited glutamine synthetase function ( Guillemin, 2012 ). QA in complex with Fe 3+ also results in oxidative damage to lipids ( Goda et al, 1996 ; Stípek et al, 1997 ; Guillemin, 2012 ). Elevated QA levels have previously been identified in cases of HIV-associated neurological damage ( Heyes et al, 2001 ), Alzheimer's disease ( Guillemin et al, 2003 ), multiple sclerosis ( Aeinehband et al, 2016 ).…”

Section: Immunity Kyn Pathway Metabolites and De Novo Nad + Metabolismmentioning

confidence: 99%

NAD+ Metabolism, Metabolic Stress, and Infection

Groth

Venkatakrishnan

Lin

2021

Front. Mol. Biosci.

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Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite with wide-ranging and significant roles in the cell. Defects in NAD+ metabolism have been associated with many human disorders; it is therefore an emerging therapeutic target. Moreover, NAD+ metabolism is perturbed during colonization by a variety of pathogens, either due to the molecular mechanisms employed by these infectious agents or by the host immune response they trigger. Three main biosynthetic pathways, including the de novo and salvage pathways, contribute to the production of NAD+ with a high degree of conservation from bacteria to humans. De novo biosynthesis, which begins with l-tryptophan in eukaryotes, is also known as the kynurenine pathway. Intermediates of this pathway have various beneficial and deleterious effects on cellular health in different contexts. For example, dysregulation of this pathway is linked to neurotoxicity and oxidative stress. Activation of the de novo pathway is also implicated in various infections and inflammatory signaling. Given the dynamic flexibility and multiple roles of NAD+ intermediates, it is important to understand the interconnections and cross-regulations of NAD+ precursors and associated signaling pathways to understand how cells regulate NAD+ homeostasis in response to various growth conditions. Although regulation of NAD+ homeostasis remains incompletely understood, studies in the genetically tractable budding yeast Saccharomyces cerevisiae may help provide some molecular basis for how NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function and how they are regulated by various nutritional and stress signals. Here we present a brief overview of recent insights and discoveries made with respect to the relationship between NAD+ metabolism and selected human disorders and infections, with a particular focus on the de novo pathway. We also discuss how studies in budding yeast may help elucidate the regulation of NAD+ homeostasis.

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“…In connection with this, it has been shown that QUIN can produce oxidative damage independent of its effects exerted via the NMDA receptor; this mechanism involves the formation of a complex of QUIN and Fe 2+ . The QUIN-Fe 2+ complex has been shown to induce intensive free radical formation likely responsible for in vitro lipid peroxidation and DNA damage (Goda et al, 1996). Additionally, there is evidence that QUIN can enhance free radical production through the induction of NOS activity in astrocytes and neurons which also leads to oxidative stress (Braidy et al, 2010): during neuroinflammation, activated microglia and QUIN produced by macrophages can enhance-via the activation of the NMDA receptor-the activity of NOS enzyme activity in astrocytes and neurons resulting in enhanced nitric oxide (NO) production [see review (Lugo-Huitrón et al, 2013)].…”

Section: Mitochondrial Dysfunction and Oxidative Stressmentioning

confidence: 99%

Kynurenines and Neurofilament Light Chain in Multiple Sclerosis

et al. 2021

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Multiple sclerosis is an autoimmune, demyelinating, and neurodegenerative disease of the central nervous system. In recent years, it has been proven that the kynurenine system plays a significant role in the development of several nervous system disorders, including multiple sclerosis. Kynurenine pathway metabolites have both neurotoxic and neuroprotective effects. Moreover, the enzymes of the kynurenine pathway play an important role in immunomodulation processes, among others, as well as interacting with neuronal energy balance and various redox reactions. Dysregulation of many of the enzymatic steps in kynurenine pathway and upregulated levels of these metabolites locally in the central nervous system, contribute to the progression of multiple sclerosis pathology. This process can initiate a pathogenic cascade, including microglia activation, glutamate excitotoxicity, chronic oxidative stress or accumulated mitochondrial damage in the axons, that finally disrupt the homeostasis of neurons, leads to destabilization of neuronal cell cytoskeleton, contributes to neuro-axonal damage and neurodegeneration. Neurofilaments are good biomarkers of the neuro-axonal damage and their level reliably indicates the severity of multiple sclerosis and the treatment response. There is increasing evidence that connections exist between the molecules generated in the kynurenine metabolic pathway and the change in neurofilament concentrations. Thus the alterations in the kynurenine pathway may be an important biomarker of the course of multiple sclerosis. In our present review, we report the possible relationship and connection between neurofilaments and the kynurenine system in multiple sclerosis based on the available evidences.

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Quinolinic Acid and Active Oxygens

Cited by 54 publications

References 11 publications

Toxin-Induced Experimental Models of Learning and Memory Impairment

Toxin-Induced Experimental Models of Learning and Memory Impairment

NAD+ Metabolism, Metabolic Stress, and Infection

Kynurenines and Neurofilament Light Chain in Multiple Sclerosis

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