Fig. 9: | Nature Communications

Fig. 9

From: TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons

Fig. 9

GR regulation of TLR9 activation in microglia that impacts dopamine neuron death. In Parkinson’s disease, chronically high cortisol levels likely compromise GR activity in innate immune cells. TLR9 levels are modulated in post-mortem Parkinson disease brains. Reduced GR activity in microglia permits activation of TLR9 by DAMPS such as CpG-rich mitochondrial DNA released from affected dopamine neurons that selectively exacerbates dopamine neuronal loss in substantia nigra. In microglia, intact GR activity acts as a brake for TLR9 activation and downstream inflammatory gene expression by regulating TLR9 trafficking through expression of UNC93B1 and progranulin and AEP-mediated cleavage of TLR9