DJ-1 in astrocytic neuroprotection to oxidative stress

Abstract Astrocytes are vital for maintaining and regulating redox environments in the brain. Astrocytic protection extends in a transcellular action toward the neurons, which are highly sensitive to oxidative stress. The complete mechanism of astrocytic neuroprotection has yet to be elucidated; however, astrocytic DJ-1 appears to play a vital role in this neuroprotective effect. High levels of DJ-1 in astrocytes surrounding pathological areas observed in a number of neurodegenerative diseases support a key role of astrocytic DJ-1 in oxidative stress response. Astrocytic DJ-1 can act as an intracellular sensor of oxidative stress from reactive oxygen/nitrogen species. In animal models, increased astrocytic DJ-1 levels have been shown to be neuroprotective to oxidative stressors. The mechanisms of this neuroprotection appear to be multifaceted including: suppression of proapoptotic signaling, activating the Nrf2/Keap1 pathway, controlling mitochondrial turnover, and regulating astrogliosis and inflammatory pathways.