Quinolinic acid, the inescapable neurotoxin

@article{Guillemin2012QuinolinicAT,
  title={Quinolinic acid, the inescapable neurotoxin},
  author={Gilles J. Guillemin},
  journal={The FEBS Journal},
  year={2012},
  volume={279}
}
  • G. Guillemin
  • Published 1 April 2012
  • Biology, Chemistry
  • The FEBS Journal
Over the last two decades, evidence for the involvement of quinolinic acid (QUIN) in neuroinflammatory diseases has been exponentially increasing. Within the brain, QUIN is produced and released by infiltrating macrophages and activated microglia, the very cells that are prominent during neuroinflammation. QUIN acts as an agonist of the N‐methyl‐d‐aspartate receptor and as such is considered to be a brain endogenous excitotoxin. Since the discovery of the excitotoxic activity of QUIN in the… 
Characterization of the Kynurenine Pathway and Quinolinic Acid Production in Macaque Macrophages
TLDR
The simian model as a relevant model to study the human cellular KP metabolism in the context of inflammation is validated, and the KP profiles in simian macrophages were very similar to those in humans when challenged with inflammatory cytokines.
Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
TLDR
Some of the chemical strategies for the modification of the kynurenine pathway are identified, with examples of their successful application in animal models of infection, stroke, traumatic brain damage, cerebral malaria and cerebral trypanosomiasis.
Neuroprotective Effect of Myxobacterial Extracts on Quinolinic Acid-Induced Toxicity in Primary Human Neurons
TLDR
The results showed that some myxobacterial extracts can significantly attenuate formation of reactive oxygen species (ROS), nitric oxide (NO) production, and extracellular lactate dehydrogenase (LDH) activity of human neurons, and some extracts were also able to reduce neuronal Nitric oxide synthase (nNOS) activity.
Quinolinic acid toxicity on oligodendroglial cells: relevance for multiple sclerosis and therapeutic strategies
TLDR
This study examines the kynurenine pathway (KP) profile of two oligodendrocyte cell lines and shows that these cells have a limited threshold to catabolize exogenous quinolinic acid, providing a new insight into therapeutic strategies for limiting quinolic acid-induced neurodegeneration, especially in neurological disorders that target oligodendedrocytes, such as MS.
The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum
TLDR
The results of this study show a neuroprotective role and antioxidant action of LVT against the brain damage induced by excitotoxic events.
Involvement of the kynurenine pathway in the pathogenesis of Parkinson’s disease
Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum
TLDR
The ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture is described to elucidate the molecular basis of KYNA protection against QUIN toxicity.
Quinolinic Acid Impairs Redox Homeostasis, Bioenergetic, and Cell Signaling in Rat Striatum Slices: Prevention by Coenzyme Q10.
TLDR
CoQ10 may be a promising therapeutic alternative for neuroprotection against QUIN neurotoxicity, and is suggested to be an important antioxidant and anti-inflammatory action.
Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices
TLDR
KYNA prevents changes in Nrf2 levels, oxidative imbalance, and mitochondrial dysfunction caused by QUIN in striatal slices, and elucidates some of the protective effects of KYNA against the damage caused by quinolinic acid toxicity.
Does kynurenic acid act on nicotinic receptors? An assessment of the evidence
  • T. Stone
  • Biology
    Journal of neurochemistry
  • 2019
TLDR
There is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors, and since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, results with kynUREnic acid should be interpreted only in terms of these confirmed sites of action.
...
...

References

SHOWING 1-10 OF 126 REFERENCES
Implications for the Kynurenine Pathway and Quinolinic Acid in Amyotrophic Lateral Sclerosis
TLDR
The kynurenine pathway is a major route of L-tryptophan catabolism leading to production of several neurobiologically active molecules and most of the factors associated with QUIN toxicity are found in ALS, implying that QUIN may play a substantial role in the neuropathogenesis of ALS.
Mechanism for Quinolinic Acid Cytotoxicity in Human Astrocytes and Neurons
TLDR
Quin-induced cytotoxic effects on neurons and astrocytes are likely to be mediated by an over activation of an NMDA-like receptor with subsequent induction of NOS and excessive nitric oxide (NO•)-mediated free radical damage.
Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in Alzheimer's disease hippocampus
TLDR
Evidence that the kynurenine pathway is up‐regulated in Alzheimer's disease (AD) brain, leading to increases in the excitotoxin quinolinic acid (QUIN) is provided, implying that QUIN may be involved in the complex and multifactorial cascade leading to neuro‐degeneration in AD.
Quinolinic acid in the pathogenesis of Alzheimer's disease.
TLDR
Data imply that QUIN may be, locally, one of the factors involved in the pathogenesis of neuronal damage in AD, and the potential modulatory effect of QUIN and kynurenic acid (KYNA) on Abeta11-42 and Abeta1-40 aggregation is investigated.
Expression of indoleamine 2,3‐dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons
TLDR
It is found that astrocytes, neurons, and microglia expressed IDO but onlymicroglia were able to produce detectable amounts of QUIN, and the first evidence of IDO expression and lack of production ofQUIN in culture of primary human neurons is provided.
Neuropharmacology of quinolinic and kynurenic acids.
  • T. Stone
  • Biology
    Pharmacological reviews
  • 1993
TLDR
Whatever the specific nature of their physiological roles, the presence of an endogenous selective agonist and antagonist acting at NMDA receptors must continue to present exciting possibilities for understanding the pathological basis of several CNS disorders as well as developing new therapeutic approaches.
Expression of the kynurenine pathway enzymes in human microglia and macrophages.
TLDR
Results suggest that activated infiltrating macrophages are the most potent QUIN producers during brain inflammatory diseases with playing a lesser role.
Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease
TLDR
It is shown that QUIN is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.
Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection
TLDR
Some of the chemical strategies for the modification of the kynurenine pathway are identified, with examples of their successful application in animal models of infection, stroke, traumatic brain damage, cerebral malaria and cerebral trypanosomiasis.
The quinolinic acid hypothesis in Huntington's chorea
...
...