Neuron–microglia interactions in neuroinflammation

Neuron–microglia interactions play pivotal roles in the development and maintenance of the central nervous system. Microglia promote synaptic pruning in the developing brain and survey neuronal activity in the mature brain. Neurons regulate microglial function through the production of various cytokines and chemokines. In central nervous system diseases, including neurodegenerative diseases, demyelinating disease and brain ischemia, neuroinflammation induced by activated microglia contributes to the disruption of beneficial neuron–microglia interactions. Activated microglia exert neurotoxicity by producing pro‐inflammatory cytokines, glutamate and reactive oxygen species. Damaged neurons release soluble factors known as “eat me” signals, which enhance microglial phagocytosis and inflammatory response. However, damaged neurons also suppress microglial activation through the induction of anti‐inflammatory cytokines and chemokines, thereby reducing neuroinflammation. Here, the roles of neurons and microglia in neuroinflammation in Alzheimer's disease are reviewed.