'STING' protein's efforts to clean up brain cell damage may
In studies with mouse and human tissue, as well as live mice, Johns Hopkins Medicine researchers report that a snag in the normal process of cleaning up broken DNA in brain cells may hasten the progression of Parkinson's disease. Specifically, the researchers found that a protein dubbed "STING" responds to cleanup signals in brain cells damaged by Parkinson's disease by creating a cycle of inflammation that may accelerate the disease's progression.

As part of this immune response, the STING protein—STING stands for stimulator of interferon genes—initiates a cascade of inflammatory chemical signals that bring immune cells to the site to clean up the damaged DNA. While this response may be beneficial to destroying viruses and bacteria in the rest of the body, the researchers suspect such an inflammatory response in the brain may disrupt the delicate balance of brain cell signals, leading to a worsening of Parkinson's disease.

The researchers suspected that the inflammatory response initiated by STING might send the microglia's immune response into overdrive because of internal DNA damage. The response, the researchers suggest, may trigger microglia to unnecessarily destroy more dopamine neurons. Upon examining the brain tissue of mice injected with misfolded alpha-synuclein, the researchers found that mice with deactivated STING proteins had less microglial activity and brain cell death. These mice also performed better in physical tasks of strength and movement used to examine Parkinson's disease progression in mice. The team also examined the brain tissue of people who died with Parkinson's disease, and found elevated levels of STING in their brain tissues.

Source: https://www.pnas.org/doi/abs/10.1073/pnas.2118819119