Scientists at Johns Hopkins Medicine have identified a promising new therapeutic target for Alzheimer’s disease: Cystathionine γ-lyase (CSE), an enzyme responsible for producing trace amounts of hydrogen sulfide in the brain. The findings come from a National Institutes of Health–funded study published on December 26 in the Proceedings of the National Academy of Sciences (PNAS).
The research suggests that CSE plays a central role in memory formation and overall brain health, opening a potential new pathway for slowing neurodegenerative disease.
🧠 Why CSE Matters in the Brain #
CSE is best known for producing hydrogen sulfide—the gas associated with the smell of rotten eggs. While toxic at high concentrations, extremely small amounts of hydrogen sulfide act as a neuroprotective signaling molecule in the brain.
According to study leader Bindu Paul, Ph.D., associate professor at the Johns Hopkins University School of Medicine, direct delivery of hydrogen sulfide is unsafe. Instead, enhancing the brain’s own ability to regulate the gas through CSE may offer a safer and more precise therapeutic strategy.
🧪 What the Mouse Experiments Revealed #
Using genetically engineered mice that lack the CSE enzyme, researchers uncovered striking Alzheimer’s-like changes:
- Progressive memory and learning impairment
- Increased oxidative stress and DNA damage
- Breakdown of blood–brain barrier integrity
- Reduced formation of new neurons in the hippocampus
These features closely mirror hallmark pathological changes seen in Alzheimer’s disease.
🧭 Progressive Memory Loss Linked to CSE Deficiency #
To assess spatial memory, scientists used the Barnes maze, a standard behavioral test that measures learning and navigation.
- At two months, both normal mice and CSE-deficient mice successfully learned the task.
- By six months, CSE-deficient mice could no longer locate the escape route, while normal mice retained the ability.
“The decline in spatial memory indicates a progressive neurodegenerative process that we can directly attribute to CSE loss,” says first author Suwarna Chakraborty.
🧬 Disrupted Neurogenesis and Brain Structure #
Further analysis showed that mice lacking CSE expressed far fewer proteins involved in neurogenesis, the process by which new neurons are formed. High-resolution electron microscopy also revealed:
- Structural breaks in brain blood vessels
- Damage to the blood–brain barrier
- Impaired migration of new neurons into the hippocampus
“These mice were compromised at multiple biological levels,” says co-first author Sunil Jamuna Tripathi, “closely matching what we see in Alzheimer’s pathology.”
🔬 Building on a Decade of Research #
This study builds on earlier work from Solomon Snyder, M.D., who first linked CSE to brain health in 2014 in models of Huntington’s disease. Subsequent research showed that CSE function is impaired in Alzheimer’s models and that tiny amounts of hydrogen sulfide could partially protect neurons.
What distinguishes the current study is its focus on CSE alone, independent of other disease-causing genetic mutations.
“CSE itself is a major driver of cognitive function,” Snyder notes. “That makes it a compelling new target for Alzheimer’s treatment strategies.”
🌍 Why This Matters #
More than 6 million people in the United States are currently living with Alzheimer’s disease, and no therapy has been shown to reliably halt disease progression. By identifying CSE as a central regulator of memory, vascular integrity, and neuronal health, this research opens the door to:
- Drugs that boost CSE expression or activity
- Safer modulation of hydrogen sulfide signaling
- Earlier intervention in neurodegenerative disease
🧩 Conclusion #
The discovery of CSE’s fundamental role in cognition represents a meaningful shift in Alzheimer’s research. Rather than targeting amyloid plaques or tau proteins alone, future therapies may focus on restoring the brain’s intrinsic protective chemistry.
While clinical applications remain years away, CSE now stands out as a promising and biologically grounded target in the ongoing search for effective Alzheimer’s treatments.