Science News

from research organizations

This “rotten egg” brain gas could be the key to fighting Alzheimer’s disease

Researchers found that a protein responsible for producing trace amounts of hydrogen sulfide is essential for memory and brain health.

Date:

April 8, 2026

Source:

Johns Hopkins Medicine

Summary:

Scientists have uncovered a surprising new player in Alzheimer’s disease: a protein called CSE that helps produce tiny amounts of hydrogen sulfide gas in the brain. In experiments with genetically engineered mice, removing this protein led to memory loss, brain damage, and other hallmarks of Alzheimer’s, including weakened blood-brain barriers and reduced formation of new neurons. The findings suggest that this “rotten egg” gas, when carefully regulated, may actually protect brain cells and support memory.

Facebook

Twitter

FULL STORY

A confocal microscopy image of doublecortin-stained newborn neurons (pink) and nuclear stain DAPI (green), which shows that neurogenesis is occurring in the brain of a normal mouse. Credit: Sunil Jamuna Tripathi

Researchers at Johns Hopkins Medicine report that a newly funded study by the National Institutes of Health is helping advance a potential new approach to Alzheimer's disease treatment. The focus is a protein in the brain that produces a small but important gas.

The protein, called Cystathionine γ-lyase, or CSE -- best known for generating hydrogen sulfide, the gas that smells like rotten eggs -- appears to play a key role in how memory forms. The findings come from experiments in genetically engineered mice, according to study leader Bindu Paul, M.S., Ph.D., associate professor of pharmacology, psychiatry and neuroscience at the Johns Hopkins University School of Medicine.

The research, published in Proceedings of the National Academy of Sciences, aims to better understand how this protein works and whether boosting its activity could help protect brain cells and slow neurodegenerative diseases such as Alzheimer's.

Hydrogen Sulfide May Protect Brain Cells

Earlier studies suggested that hydrogen sulfide can help protect neurons in mice. However, the gas is toxic in large amounts, which makes it unsafe to deliver directly to the brain. Scientists are instead trying to understand how to safely maintain the extremely small levels naturally present in neurons.

The new findings show that mice engineered to lack the CSE enzyme develop problems with memory and learning. These mice also show increased oxidative stress, DNA damage and weakened blood-brain barrier integrity -- all features commonly associated with Alzheimer's disease, says Paul, the study's corresponding author.

Building on Years of Research

The current work builds on earlier research led by Solomon Snyder, M.D., D.Sc., D.Phil., professor emeritus of neuroscience, pharmacology, and psychiatry. In 2014, his team reported that CSE supported brain health in mice with Huntington's disease. The researchers used mice lacking the CSE protein, first developed in 2008 when the protein was linked to blood vessel function and blood pressure regulation.

In 2021, the group found that CSE was not functioning properly in mice with Alzheimer's disease, and that very small injections of hydrogen sulfide helped protect brain function.

Those earlier studies focused on mice with additional genetic mutations tied to neurodegenerative diseases. The latest research isolates the role of CSE itself.

"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," says co-corresponding author Snyder, who retired from the Johns Hopkins Medicine faculty in 2023.

Memory Loss Linked to CSE Deficiency

To better understand how CSE affects memory, scientists compared mice lacking the protein with normal mice using the same strain developed in 2008. They tested spatial memory (ability to remember directions and follow cues) using a setup called the Barnes maze.

In this test, mice learn to escape a bright light by finding a hidden shelter. At two months old, both normal mice and those lacking CSE performed similarly, locating the shelter within three minutes. By six months, however, the CSE-deficient mice struggled to find the escape route, while normal mice continued to succeed.

"The decline in spatial memory indicates a progressive onset of neurodegenerative disease that we can attribute to CSE loss," says first author Suwarna Chakraborty, a researcher in Paul's lab.

Brain Changes Mirror Alzheimer's Disease

The researchers also examined how the absence of CSE affects the brain at a cellular level. The hippocampus, a region critical for learning and memory, relies on the formation of new neurons. Disruptions in this process are a known feature of neurodegenerative diseases.

Using biochemical and analytical methods, the team found that proteins involved in neurogenesis