Fig. 1.

Schematic showing the modes of neuroinflammation in healthy and AD brain. A The healthy brain has minimal Aβ aggregates. Under normal physiological function microglia and astrocytes maintain neuronal homeostasis by clearing Aβ aggregates and providing neurotrophic factor to the brain. B The Alzheimer’s brain is associated with a large number of Aβ aggregates. The inhibited phagocytosis of Aβ aggregates and abrupt inflammatory response by microglia and astrocytes lead to the Aβ aggregates accumulation. Aβ aggregates bind to the pattern recognition receptors (PRRs) of microglia and stimulate downstream target genes NF-κB and AP-1. Subsequently, activated microglia produces cytokines. Cytokines contribute to astrocytes activation (referred to as reactive astrocytes) and affect neuronal health by causing neurotoxicity. The binding of Aβ aggregates to the microglia induces the NADPH oxidase and inducible nitric oxide synthase to produce ROS and NO leading to neurotoxicity. Likewise, Aβ aggregates bind to astrocyte receptors leading to the activation of downstream target genes NF-κB and AP-1 that subsequently produce cytokines. Cytokines affect neuronal health and cause neurotoxicity. The Aβ aggregates induce NADPH oxidase and inducible nitric oxide to produce ROS and NO by reactive astrocytes. The abrupt cross-talk between neurons, astrocytes, and microglia involving inflammatory molecules shown in the picture causes an imbalance in brain homeostasis and promotes neuronal death