Figure 2.

Inflammation significantly shifts tryptophan metabolism to Kynurenine production by activation of activate indole-2,3-dioxygenase (IDO) and Kynurenine monooxygenase (KMO) microglial enzymes. Quinolinic acid (QUIN) is involved in neurotoxicity since it activates N-methyl-D-aspartate (NMDA) receptors, increases neuronal activity, and elevates intracellular calcium concentrations. This leads to the consequent impairment of cytoskeleton homeostasis, decrease of mitochondrial function and finally cell death induction. As an NMDA agonist, it increases neuronal glutamate release, inhibits its uptake by astrocytes, and inhibits astroglial glutamine synthetase leading to excessive microenvironmental glutamate concentrations. In addition, QUIN contributes to free radical generation and oxidative stress.