Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

Table 2

Alterations in QUIN levels presented in different neurodegenerative diseases and experimental models. Key references are shown in the quarter column.

Disease/model	QUIN levels	Associated alterations	Reference
Alzheimer	↑ in demented patient; ↑ in senile plaques	(i) IDO overexpression; (ii) ↓ KYNA; (iii) QUIN colocalizes with tau in cortical sections; (iv) ↑ QUIN/3-HK quotient in plasma	[25, 26, 91, 92]
A𝛽 1-42	↑	(i) IDO over-expression in microglia and macrophages	[93]
Huntington	↑	(i) ↑ 3-HK	[94]
Huntingtin transgenic mice	↑ in YAC128 mice, Hdh^Q92/Hdh^Q111 knock-in mice	(i) ↑ 3-HK	[95]
Human immunodeficiency virus (HIV)	↑ in CSF and serum of patients	(i) Cytokines release; (ii) ↑ IDO; (iii) QUIN levels enhanced independent blood brain barrier breakdown	[96–98]
Suicide attempters	↑ in CSF of suicide attempters	(i) An increased QUIN/KYNA quotient	[99]
Depression	↑ QUIN expression in human brain during acute depressive episodes	(i) Abnormal NMDA receptor function	[100]
Autism	↑ in CFS of patients	(i) ↑ biopterin; (ii) ↓ neopterin	[101]
Amyotrophic lateral sclerosis	↑ in CSF and serum of patients	(i) ↑ TRP and L-KYN, human leukocyte antigen-DR; (ii) IDO over-expression	[102]
Experimental allergic encephalomyelitis, a model of multiple sclerosis	↑ in the spinal cords of rats	(i) ↑ in KMO activity and 3-HK levels	[103, 104]

IDO: indolamine 2,3-dioxigenase, KYNA: kynurenic acid, QUIN: quinolinic acid, L-KYN: L-kynurenine, 3-HK: 3-hydroxykynurenine, TRP: tryptophan, and CSF: cerebrospinal fluid.