Figure 1.

Neuron-astrocyte interaction under neuropathological conditions. Neurotoxic A1 astrocytes, induced by activated microglia, upregulate proinflammatory factors, such as IL-1α, IL-1β and TNF-α and produce neuroinflammation. Microglia-released proinflammatory mediators, such as TNF-α, IL-1β, and IFN-γ, inhibit glutamate uptake in astrocytes leading to glutamate toxicity. Nrf2 system disruption in astrocytes leads to decrease in antioxidative molecules, which results in oxidative stress. Damaged neurons release aggregated α-synuclein and damaged mitochondria. Neuron-to-astrocyte transmission of α-synuclein, followed by its accumulation and deposition in astrocytes, produces proinflammatory cytokines and impairs glutamate uptake via GLT-1.