Figure 1.

Microglia response to chronic peripheral inflammation may alter the state of neighboring cells.

Cells of the innate and adaptive immune system (e.g., monocytes, dendritic cells, T and B cells) may directly migrate into the central nervous system and inflammatory mediators like cytokines (e.g., tumor necrosis factor alpha (TNFα), interleukin-1β, and interleukin-6) may also indirectly activate endothelial cells or perivascular macrophages. Changes in the environment are sensed by microglia. Microglia may secrete cytokines or reactive oxygen species (ROS) or reactive nitrogen species (RNS), which affect nearby astrocytes, oligodendrocytes, endothelial cells of blood vessels, and neurons. These events can lead to impaired phagocytosis of protein aggregates like amyloid plaques and eventually to neuronal dysfunction, synaptic degeneration, and neuronal loss. Figure 1 was created using BioRender (https://biorender.com).