Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

Figure 2

Multiple mechanisms leading to QUIN cytotoxicity. One of the principal toxicity mechanism of QUIN is through the over stimulation of the NMDA receptor which is powered by the lack of uptake of QUIN from the extracellular space. Additionally, QUIN enhances the release of synaptosomal glutamate as a consequence of the inhibition of glutamate uptake into the astrocytes that will lead to overstimulation of receptors. Furthermore, QUIN can decrease the activity of antioxidant enzymes promoting ROS production and generating lipid peroxidation. Also, QUIN may inhibit the activity of mitochondrial complexes leading to energetic deficit, activating caspases and releasing cytochrome c. All these factors induce cytoskeleton destabilization, DNA damage, and cell death.