Toxic fatty acids responsible for brain cell death after injury

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New studies in rodents show that cells that normally nourish healthy brain cells, called neurons, release toxic fatty acids after neurons are damaged. Researchers say this phenomenon is likely to be the driving force behind most, if not all, diseases that affect brain function, as well as the natural destruction of brain cells seen with aging. Said.

Previous studies have indicated that stellate cells, the stellate glial cells of the central nervous system, are a cause of cell death in Parkinson’s disease, dementia and other neurodegenerative diseases. Many experts believed that these cells release molecules that kill neurons in order to “clean” damaged brain cells, but the identity of this toxin has so far remained a mystery.

A new study by researchers at NYU Grossman School of Medicine says this is the first evidence that tissue damage stimulates stellate cells to produce two types of fat, long-chain saturated free fatty acids and phosphatidylcholine. Offers. These fats cause cell death in damaged neurons, the electrically active cells that send messages throughout nerve tissue.

Published on October 6 in the journal Nature, the study also showed that when researchers blocked fatty acid formation in mice, 75% of neurons survived, compared to 10% when fatty acids did. Previous research by researchers has shown that brain cells continue to function when protected. Attack of astrocytes.

“Our results show that toxic fatty acids produced by astrocytes play an important role in brain cell death, providing promising new targets for the treatment and possibly prevention of many neurodegenerative diseases. “It shows,” said Dr. Shane Redero, lead co-author of the study. NS.

Liddelow, assistant professor of neuroscience and physiology at NYU Langone Health, adds that targeting these fats, rather than the cells that produce them, may be a safer treatment approach. Neurodegenerative diseases Because astrocytes nourish nerve cells and eliminate their wastes. Keeping them from working fully can interfere with your health Brain function.

It’s unclear why astrocytes produce these toxins, but Redraw says they can evolve and destroy damaged cells before harming their neighbors. Although it is a healthy cell Because they are not damaged by toxins, neurons are susceptible to damage when damaged, mutated or infected with prions, a contagious misfolded protein which plays a major role in mad cow disease and similar diseases. to augment. Perhaps in chronic diseases such as dementia, helpful processes fail to start and become a problem, according to the study’s authors.

For the research, the researchers analyzed molecules released by astrocytes collected from rodents. They also genetically modified several groups of mice to prevent the normal production of toxic fats and studied whether neuronal death occurred after acute injury.

“Our results provide what is probably the most detailed molecular map to date of how tissue damage is linked. brain Cell deathTo help researchers better understand why Neuron You will die from all kinds of diseases, ”says Redero, assistant professor of ophthalmology at NYU Langone.

Liddelow warns that while the results are promising, the genetic technology used to block enzymes that produce toxic fatty acids in mice is not ready for use in humans. As a result, the researchers’ next plan is to find safe and effective ways to prevent the release of toxins in human patients. Liddelow and his colleagues had previously shown these neurotoxic astrocytes in the brains of patients with Parkinson’s disease and Huntington’s disease. disease, and, among other diseases, multiple sclerosis.

Star-shaped brain cells may play an important role in glaucoma

For more information: Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 2021. DOI: 10.1038 / s41586-021-03960-y, www.nature.com/articles/s41586-021-03960-y

Provided by NYU Langone Health

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