Fig. 3

Schematic of microglial activation, astrocyte activation, and their relationship. The pro-inflammatory phenotypes are neurotoxic, while the neuroprotective phenotypes are neuroprotective. CHF 5074 polarizes microglia from the pro-inflammatory to the neuroprotective phenotype. Microglia can switch from the neuroprotective to the pro-inflammatory phenotype in the context of type 2 diabetes, obesity, and insulin resistance. Some candidates (dimethyl fumarate, fasudil, minocycline, and copaxone) can potentiate the neuroprotective polarity of microglia. The pro-inflammatory microglia secret IL-1α, IL-1β, TNF-α, and C1q, which can change astrocytes into the pro-inflammatory phenotype. The pro-inflammatory astrocytes secret CCL2, CX3CL1, CXCL10, GM-CSF, and IL-1, which in turn activate the pro-inflammatory microglia. The phenotype transition of astrocytes remains to be clarified. The dotted lines with question marks represent a possible relationship, with a lack of evidence for direct association. M: resting microglia; A: astrocytes. Other abbreviations as in Fig. 2