Researchers at Johns Hopkins Medicine have identified a protein that produces hydrogen sulfide—a gas typically known for its rotten egg odor—as a critical component in protecting brain health and preventing Alzheimer’s-related decline. The study, published in the Proceedings of the National Academy of Sciences, suggests that maintaining precise levels of this gas could offer a new pathway for neurodegenerative disease treatment.
The protein, known as Cystathionine γ-lyase (CSE), generates tiny amounts of hydrogen sulfide in the brain. While the gas is notoriously toxic in high concentrations, lead researcher Bindu Paul notes that naturally occurring, trace amounts are vital for cognitive stability.
The role of CSE in memory
To test the protein's function, scientists utilized genetically engineered mice lacking the CSE enzyme. While the mice appeared healthy at two months old, they began to show significant cognitive deficits by the six-month mark. During testing in a Barnes maze, which tracks spatial memory, the CSE-deficient mice struggled to locate escape routes compared to their healthy counterparts.
"The decline in spatial memory indicates a progressive onset of neurodegenerative disease that we can attribute to CSE loss," said first author Suwarna Chakraborty. Beyond memory loss, the team observed increased oxidative stress and structural damage to the blood-brain barrier in the CSE-deficient subjects.
Microscopic analysis revealed that the absence of the protein disrupted the formation of new neurons in the hippocampus, a brain region essential for learning. This process, known as neurogenesis, is frequently impaired in patients suffering from Alzheimer’s.
Developing a therapy based on these findings remains a complex challenge. Because hydrogen sulfide is dangerous in large doses, researchers are focused on how to safely regulate the gas within neurons rather than delivering it directly.
This research builds on a decade of work involving CSE. In 2021, the same team observed that the protein malfunctioned in mice with Alzheimer’s, and that targeted, minute injections of hydrogen sulfide helped preserve brain function. Solomon Snyder, a professor emeritus who co-authored the study, believes the new findings confirm that CSE is a primary player in cognitive health.
"This most recent work indicates that CSE alone is a major player in cognitive function and could provide a new avenue for treatment pathways in Alzheimer's disease," Snyder said.
