Interactions between microglia and astrocytes and mechanisms of damage to dopaminergic neurons

Both microglia and astrocytes have differentiated pro-inflammatory phenotypes that are neurotoxic and injurious to dopaminergic neurons, whereas the neuroprotective phenotypes are neuroprotective and protective of dopaminergic neurons. Under certain specific circumstances, the pro-inflammatory and anti-inflammatory phenotypes of microglia can be switched. Pro-inflammatory microglia secrete interleukin-1 alpha (IL-1a), interleukin 1 beta (IL-1b), tumor necrosis factor-alpha (TNF-a), and complement component 1q (C1q), which can convert astrocytes to a pro-inflammatory phenotype. Pro-inflammatory astrocytes secrete IL-1b, TNF-a, granulocyte-macrophage colony-stimulating factor (GM-CSF), and chemokine C-C motif ligand 2 (CCL2), which in turn activate pro-inflammatory microglia. The phenotypic transition of astrocytes remains to be clarified. Dashed lines with question marks indicate possible relationships, but evidence of a direct association is lacking. (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.)