Figure 5: The possible role of Kynurenine pathway involvement in dopaminergic neurodegenerative process through microglia activation: Parkinson’s disease is associated with chronic activation of microglia, which also can be induced by LPS or Rotenone treatments. Classic microglia activation release neurotoxic substances including reactive oxygen species (ROS) and proinflammatory cytokines as INF-γ, potent activator of Kynurenine pathway (KP). KP in activated microglia leads to upregulation of 3HK and QUIN. 3HK is toxic primarily as a result of conversion to ROS. The combined effects of ROS and NMDA receptor-mediated excitotoxicity by QUIN contribute to the dysfunction of neurons and their death. However, picolinic acid (PIC) produced through KP activation in neurons, has the ability to protect neurons against QUIN-induced neurotoxicity, being NMDA agonist. Microglia can become overactivated, by proinflammatory mediators and stimuli from dying neurons and cause perpetuating cycle of further microglia activation microgliosis. Excessive microgliosis will cause neurotoxicity to neighbouring neurons and resulting in neuronal death, contributing to progression of Parkinson’s disease.