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Clinical Implications[edit]

Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS)[edit]

Studies have found that there is a correlation between levels of QUIN in cerebral spinal fluid (CSF) and HIV associated neurocognitive disorder (HAND) severity. About 20% of HIV patients suffer from this disorder. Concentrations of QA in the CSF are associated to different stages of HAND. For example, raised levels of QUIN after infection are correlated to perceptual-motor slowing in patients. Then, in later stages of HIV, increased concentrations of QUIN in the of HAND patients CSF correlates with HIV encephalitis and cerebral atrophy.[1]

QUIN has also been found in HAND patients’ brains. In fact, the amount of QUIN found in the brain of HAND patients can be up to 300 times greater than that found in the CSF.[2] Neurons exposed to QA for long periods of time can develop cytoskeletal abnormalities, vacuolization, and cell death. HAND patients’ brains contain many of these defects. Furthermore, studies in rats have demonstrated that QUIN can lead to neuronal death in brains structures that are affected by HAND, including the striatum, hippocampus, the substantia nigra, and non-limbic cortex.[1]

Levels of QUIN in the CSF of AIDS patients suffering from AIDS- dementia can be up to twenty times higher than normal. Similar to HIV patients, this increased QUIN concentration correlates with cognitive and motor dysfunction. When patients were treated with zidovudine to decrease QA levels, the amount of neurological improvement was related to the amount of QUIN decreased.[2]

Mood Disorders[edit]

The prefrontal cortexes in the post-mortem brains of patients with major depression and bipolar depression contain increased levels QUIN immunoreactivity compared to the brains of patients who never suffered from depression. There is also evidence that increased concentrations of QUIN can play a role in adolescent depression.[3]

Conditions Related to Neuronal Death[edit]

Inflammation occurs at the sites of cell death which can lead to further neuronal damage. The inflammation response includes the generation of QUIN, and this QUIN contributes to the process of delayed degeneration of the neurons at the initial site of cell death.[3]

Amyotrophic Lateral Sclerosis (ALS)[edit]

QUIN may contribute to the causes of amyotrophic lateral sclerosis ALS. Researchers have found elevated levels of QUIN in the cerebral spinal fluid (CSF), motor cortex, and spinal cord in ALS patients. These increased concentrations of QUIN could lead to neurotoxicity. In addition, QUIN is associated with overstimulating NMDA receptors on motor neurons. Studies have demonstrated that QUIN leads to depolarization of spinal motor neurons by interacting with the NMDA receptors on those cells in rats. Lastly, QUIN plays a role in mitochondrial dysfunction in neurons. All of these effects could contribute to ALS symptoms.[4]

Alzheimer’s Disease[edit]

Researchers have found a strong correlation between QUIN and Alzheimer’s disease. For example, studies have found in the post-mortem brains of Alzheimer’s disease patients higher neuronal QUIN levels and that QUIN can associate with tau protein. Furthermore, researchers have demonstrated that QUIN increases tau phosphorylation in vitro in human fetal neurons and induces ten neuronal genes including some known to correlate with Alzheimer’s disease.[5]

Huntington’s Disease[edit]

Researchers utilize QUIN in order to study Huntington’s disease in many model organisms. Because injection of QUIN into the striatum of rodents induces electrophysiological, neuropathological, and behavioral changes similar to those found in Huntington’s disease, this is the most common method researchers use to produce a Huntington’s disease phenotype.[3] Neurological changes produced by QUIN injections include altered levels of glutamate, GABA, and other amino acids. Lesions in the pallidum can suppress effects of QUIN in monkeys injected with QUIN into their striatum. In humans, such lesions can also diminish some of the effects of Huntington’s disease and Parkinson’s disease.[2]

Brain Ischemia[edit]

Brain ischemia is insufficient blood flow to the brain. Studies with ischaemic gerbils indicate that after a delay levels of QUIN significantly increase which correlates with increased neuronal damage.[3]

Parkinson's Disease[edit]

Studies show that QUIN is involved in the degeneration of the dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease patients. Substantia nigra degeneration is one of the key characteristics of Parkinson's disease. Microglia associated with dopaminergic cells in the SN produce QUIN at this location when scientists induce Parkinson's disease symptoms in macaques. QUIN levels are too high at these sites to be controlled by KYNA, causing neurotoxicity to occur. [4]


QUIN levels are increased in the brains of children infected with a range of bacterial infections of the central nervous system (CNS), of poliovirus patients, and of Lyme disease with CNS involvement patients. In addition, raised QUIN levels have been found in traumatic CNS injury patients, patients suffering from cognitive decline with ageing, hyperammonaemia patients, hypoglycaemia patients, and systemic lupus erythematosus patients. Lastly, it has been found that people suffering from malaria and patients with olivopontocerebellar atrophy have raised QA metabolism.[2]


  1. ^ a b Kandanearatchi, Apsara; Brew, Bruce J. (2012). "The kynurenine pathway and quinolinic acid: pivotal roles in HIV associated neurocognitive disorders". FEBS Journal. 279 (8): 1366–1374. doi:10.1111/j.1742-4658.2012.08500.x. PMID 22260426. Retrieved 5 November 2012.  Cite uses deprecated parameter |coauthors= (help); Unknown parameter |month= ignored (help)
  2. ^ a b c d Stone, Trevor W. (2001). "Endogenous neurotoxins from tryptophan". Toxicon. 39 (1): 61–73. doi:10.1016/S0041-0101(00)00156-2. PMID 10936623. Retrieved 5 November 2012.  Unknown parameter |month= ignored (help)
  3. ^ a b c d Myint, Aye M. (2012). "Kynurenines: from the perspective of major psychiatric disorders". FEBS Journal. 279 (8): 1375–1385. doi:10.1111/j.1742-4658.2012.08551.x. PMID 22404766. Retrieved 5 November 2012.  Unknown parameter |month= ignored (help)
  4. ^ a b Tan, Lin; Yu, JT, Tan, L (15). "The kynurenine pathway in neurodegenerative diseases: Mechanistic and therapeutic considerations". Journal of the Neurological Sciences. 323 (1-2): 1–8. doi:10.1016/j.jns.2012.08.005. PMID 22939820. Retrieved 5 November 2012.  Unknown parameter |month= ignored (help); Cite uses deprecated parameter |coauthors= (help); Check date values in: |date=, |year= / |date= mismatch (help)
  5. ^ Severino, Patricia Cardoso; Muller, GDS, Vandresen-Filho, S, Tasca, CI (10). "Cell signaling in NMDA preconditioning and neuroprotection in convulsions induced by quinolinic acid". Life Sciences. 89 (15-16): 570–576. doi:10.1016/j.lfs.2011.05.014. PMID 21683718. Retrieved 5 November 2012.  Unknown parameter |month= ignored (help); Cite uses deprecated parameter |coauthors= (help); Check date values in: |date=, |year= / |date= mismatch (help)