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Free radical cell death switch identified

"A common molecular denominator in aging and many age-related diseases is oxidative stress," says the study's lead author Azad Bonni, MD, PhD, HMS associate professor of pathology. The skin of a bitten apple will brown because of its exposure to air, and in some ways that is a good metaphor for the damage that oxidative stress is causing to neurons and other types of cells over time.

Humans and other organisms depend on oxygen to produce the energy required for cells to carry out their normal functions. A cell's engine, the mitochondria, converts oxygen into energy. But this process also leaves a kind of exhaust product known as free radicals. When free radicals are not destroyed by antioxidants, they create oxidative stress. As the body ages, it produces more and more free radicals and its own antioxidants are unable to fight this process, which results in the generation of highly reactive oxygen molecules that inflict cellular damage by reacting with biomolecules including DNA, proteins, and lipids. A lifetime of oxidative stress leads to general cellular deterioration associated with aging and degenerative diseases.

How the oxidative-stress signals trigger these profound effects in cells has remained unclear. But Bonni and his research team, including Maria Lehtinen, a graduate student in the HMS program in neuroscience, and Zengqiang Yuan, PhD, an HMS research fellow in pathology, in collaboration with Keith Blackwell, MD, PhD, HMS associate professor of pathology, have now defined how a molecular chain-of-events links oxidative-stress signals to cell death in brain neurons.

In the course of investigating the mechanisms of cell death in neurons from rat brain, the team focused their attention on the function of a protein called MST, which had been previously implicated in cell death. They found that exposure of brain neurons to oxidative-stress signals stimulates the activity of MST, and once activated, MST instructs neurons to die.
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Source:Harvard Medical School


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