Hi RArmant,
             There is already an effective "drug" against
quinolinic acid in widespread use. Side effects are reductions in
cancer and longer life span. (in rodents) It has already passed
numerous phase II clinical trials for cander and Alzheimer's. At
least one large phase III trial is ongoing. The methodology of all the
completed trials was very poor. They failed to titrate dosage. Heads
would roll in any drug company trial that made such a basic error.
Despite the poor design ALL trials that I know of showed results
against both cancer and Alzheimer's!!  Some may have guessed I'm
talking another substance intimately related with and inhibitory for
the kynurenic pathway, melatonine. By the time the truth is known about
this intervention I will have been megging out on it for twenty years.
I think anyone who wakes up easily in the morning is not taking enough.

    The melatonin refs are at the bottom

Thomas

1: J Neuroinflammation. 2005 Jul 26;2(1):16 [Epub ahead of print]
Related Articles, Links
Quinolinic acid selectively induces apoptosis of human astrocytes:
potential role in AIDS dementia complex.
Guillemin GJ, Wang L, Brew BJ.
There is evidence that the kynurenine pathway (KP) and particularly one
of its end products, quinolinic acid (QUIN) play a role in the
pathogenesis of several major neuroinflammatory diseases, and more
particularly AIDS dementia complex (ADC). We hypothesized that QUIN may
be involved in astrocyte apoptosis because: 1) apoptotic astrocytes
have been observed in the brains of ADC patients, 2) ADC patients have
elevated cerebrospinal fluid QUIN concentrations, and 3) QUIN can
induce astrocyte death. Primary cultures of human fetal astrocytes were
treated with three pathophysiological concentrations of QUIN.
Numeration of apoptotic cells was assessed using double
immunocytochemistry for expression of active caspase 3 and for nucleus
condensation. We found that treatment of human astrocytes with QUIN
induced morphological (cell body shrinking) and biochemical changes
(nucleus condensation and over-expression of active caspase 3) of
apoptosis. After 24 hours of treatment with QUIN 500 nM and 1200 nM
respectively 10 and 14% of astrocytes were undergoing apoptosis. This
would be expected to lead to a relative lack of trophic support factors
with consequent neuronal dysfunction and possibly death. Astroglial
apoptosis induced by QUIN provides another potential mechanism for the
neurotoxicity of QUIN during ADC.PMID: 16042813
--------------------------------------------------------------------------------
2: Neuropathol Appl Neurobiol. 2005 Aug;31(4):395-404. Related
Articles, Links
Indoleamine 2,3 dioxygenase and quinolinic acid Immunoreactivity in
Alzheimer's disease hippocampus.
Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM.
Centre for Immunology, St Vincent's Hospital, Darlinghurst, NSW,
Australia.
             The present immunohistochemical study provides evidence
that the kynurenine pathway is up-regulated in Alzheimer's disease (AD)
brain, leading to increases in the excitotoxin quinolinic acid (QUIN).
We show that the regulatory enzyme of the pathway leading to QUIN
synthesis, indoleamine 2,3 dioxygenase (IDO) is abundant in AD compared
with controls. In AD hippocampus, both IDO- and QUIN-immunoreactivity
(-IR) was detected in cortical microglia, astrocytes and neurones, with
microglial and astrocytic expression of IDO and QUIN highest in the
perimeter of senile plaques. QUIN-IR was present in granular deposits
within the neuronal soma of AD cortex and was also seen uniformly
labelling neurofibrillary tangles. Our data imply that QUIN may be
involved in the complex and multifactorial cascade leading to
neuro-degeneration in AD. These results may open a new therapeutic door
for AD patients.PMID: 16008823
--------------------------------------------------------------------------------
3: Glia. 2005 Jan 1;49(1):15-23. Related Articles, Links
Expression of indoleamine 2,3-dioxygenase and production of quinolinic
acid by human microglia, astrocytes, and neurons.
Guillemin GJ, Smythe G, Takikawa O, Brew BJ.
Centre for Immunology, St. Vincent's Hospital, Sydney, Australia.
g.guillemin@cfi.unsw.edu.au
           There is good evidence that the kynurenine pathway (KP) and
one of its end products, quinolinic acid (QUIN) play a role in the
pathogenesis of several major neurological diseases. While QUIN has
been shown to be produced in neurotoxic concentrations by macrophages
and microglia, the capacity of astrocytes and neurons to produce QUIN
is controversial. Using interferon gamma (IFN-gamma)-stimulated primary
cultures of human mixed brain cells, we assayed expression of the KP
regulatory enzyme indoleamine 2,3-dioxygenase (IDO) and QUIN production
by immunocytochemistry. Using IFN-gamma-stimulated purified cultures of
neurons, astrocytes, microglia and macrophages, we studied IDO
expression by RT-PCR and production of QUIN using mass spectrometry. We
found that astrocytes, neurons, and microglia expressed IDO but only
microglia were able to produce detectable amounts of QUIN. However,
astrocytes and neurons had the ability to catabolize QUIN. This study
also provides the first evidence of IDO expression and lack of
production of QUIN in culture of primary human neurons. copyright (c)
2004 Wiley-Liss, Inc.PMID: 15390107
--------------------------------------------------------------------------------
4: Adv Exp Med Biol. 2003;527:167-76. Related Articles, Links
Quinolinic acid in the pathogenesis of Alzheimer's disease.
Guillemin GJ, Williams KR, Smith DG, Smythe GA, Croitoru-Lamoury J,
Brew BJ.
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
g.guillemin@cfi.unsw.edu.au
            We propose that the tryptophan catabolites produced
through the kynurenine pathway (KP), and more particularly quinolinic
acid (QUIN), may play an important role in the pathogenesis of
Alzheimer's disease (AD). In this study, we demonstrated that after 72
hours amyloid peptide (Abeta) 1-42 induced indoleamine 2,3-dioxygenase
(IDO) expression and in a significant increase in production of QUIN by
human macrophages and microglia. In contrast, Abeta11-40 and Prion
peptide (PrP) 106-126 did not induce any significant increase in QUIN
production. We also investigated the potential modulatory effect of
QUIN and kynurenic acid (KYNA) on Abeta11-42 and Abeta1-40 aggregation.
After 24 and 120 hours, we did not observe any significant difference
in the level of aggregation compared to the control (Abeta alone).
Abeta has been shown to induce IL1-beta mRNA expression by human foetal
astrocytes and macrophages. We demonstrate that QUIN has the same
effect. Interestingly, IL-1beta has been found in association with
plaques in AD. All together these data imply that QUIN may be, locally,
one of the factors involved in the pathogenesis of neuronal damage in
AD.PMID: 15206729
XXX
1:  Maharaj DS, Maharaj H, Antunes EM, Maree DM, Nyokong T, Glass BD,
Daya S. Related Articles, Links
6-Hydroxymelatonin protects against quinolinic-acid-induced oxidative
neurotoxicity in the rat hippocampus.
J Pharm Pharmacol. 2005 Jul;57(7):877-81.
PMID: 15969947 [PubMed - in process]
2:  Cabrera J, Reiter RJ, Tan DX, Qi W, Sainz RM, Mayo JC, Garcia JJ,
Kim SJ, El-Sokkary G. Related Articles, Links
Melatonin reduces oxidative neurotoxicity due to quinolinic acid: in
vitro and in vivo findings.
Neuropharmacology. 2000 Jan 28;39(3):507-14.
PMID: 10698016 [PubMed - indexed for MEDLINE]
3:  Southgate G, Daya S. Related Articles, Links
Melatonin reduces quinolinic acid-induced lipid peroxidation in rat
brain homogenate.
Metab Brain Dis. 1999 Sep;14(3):165-71.
PMID: 10646692 [PubMed - indexed for MEDLINE]
4:  Southgate GS, Daya S, Potgieter B. Related Articles, Links
Melatonin plays a protective role in quinolinic acid-induced
neurotoxicity in the rat hippocampus.
J Chem Neuroanat. 1998 Jun;14(3-4):151-6.
PMID: 9704893 [PubMed - indexed for MEDLINE]
5:  Lapin IP, Mirzaev SM, Ryzov IV, Oxenkrug GF. Related Articles,
Links
Anticonvulsant activity of melatonin against seizures induced by
quinolinate, kainate, glutamate, NMDA, and pentylenetetrazole in mice.
J Pineal Res. 1998 May;24(4):215-8.
PMID: 9572530