Mechanisms of damage to dopaminergic neurons by activated microglia

Microglia-mediated neuroinflammation and neuroprotective mechanisms in the pathogenesis of Parkinson disease. Microglia turns into an activated M1 phenotype when exposed to stimuli, such as infection, trauma, and intoxication. M1 phenotype microglia secrete pro-inflammatory factors, which further induce neuroinflammatory and neurotoxic mechanisms in the human brain through processes such as enhanced phagocytic activity and increased interleukin 1 beta (IL-1b), tumor necrosis factor-alpha (TNF-a), and reactive oxygen species (ROS) generation, damaging dopaminergic neurons. On the other hand, the presence and stimulation of anti-inflammatory factors can lead to an activated M2 phenotype. The neuroprotective mechanism of M2 microglia against Parkinson disease involves the release of anti-inflammatory cytokines into the brain and the upregulation of neuroprotective trophic factors. The anti-inflammatory cytokines include interleukin 4 (IL-4), interleukin 10 (IL-10), and so on, which inhibit persistent neuroinflammation and consequently protect the dopaminergic neurons. Disease occurs when this balance in the organism is disrupted. (Source: Zhang J, Luo L, Long E, Chen L. Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. Expert Opin Drug Saf 2023;22[8]:715-24. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)