New Insights into Proteins Controlling the Blood-Brain Barrier

Researchers develop a new technique to examine the proteins lining the inside of blood vessels, uncovering two key regulators of the critical brain-blood interface.

Apr. 10, 2026 at 4:05am

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A bold, abstract painting in muted earth tones depicting sweeping geometric forms, concentric circles, and precise botanical spirals, conceptually representing the complex biological forces and pathways that regulate the blood-brain barrier's selective permeability.A conceptual visualization of the intricate molecular mechanisms that control the selective permeability of the blood-brain barrier, a key interface regulating the exchange of substances between the bloodstream and the brain.Ashburn Today

A team led by Jiefu Li at HHMI's Janelia Research Campus has developed a new method to study all the proteins on the inner surface of blood vessels, a key interface that controls what molecules can enter and leave the brain. Using this technique, the researchers identified two proteins, SLC7A1 and HYAL2, that play a role in regulating the permeability of the blood-brain barrier, which could help inform new treatments for neurological conditions.

Why it matters

Understanding how the blood-brain barrier functions is crucial for developing better ways to deliver drugs to treat neurological diseases like Alzheimer's, Parkinson's, and multiple sclerosis, which are often blocked from entering the brain. Identifying the molecular players that control the barrier's permeability could lead to new therapeutic approaches.

The details

The researchers used their new method to examine all the proteins that make up the luminal, or inner, surface of the brain's blood vessels, which is part of the blood-brain barrier. They found that as the brain matures, proteins involved in blood vessel growth and molecule transport decrease, while aging causes the vasculature to become stiffer and less adaptable. Further testing revealed two specific proteins, SLC7A1 and HYAL2, that regulate the integrity of the blood-brain barrier - when lost, the barrier becomes leaky.

  • The research was conducted by a team led by Jiefu Li, a group leader at HHMI's Janelia Research Campus.
  • The new technique to study the proteins on the inner surface of blood vessels was developed by Li and his team.

The players

Jiefu Li

A group leader at HHMI's Janelia Research Campus who led the team that developed the new method to examine proteins on the inner surface of blood vessels.

Viviana Gradinaru

An HHMI Investigator who provided virus tools used by the research team to test how changes in the brain vasculature system affect its function.

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What they’re saying

“Understanding how the blood-brain barrier works, particularly figuring out the molecular targets that you can play with to open and close the barrier, will provide new possibilities for drug delivery.”

— Jiefu Li, Group Leader, HHMI's Janelia Research Campus

“What we know now is that we have two new pathways, potentially, to open the blood-brain barrier and to inform some therapeutic developments.”

— Jiefu Li, Group Leader, HHMI's Janelia Research Campus

What’s next

The researchers plan to further investigate how the identified proteins, SLC7A1 and HYAL2, regulate the blood-brain barrier and explore potential therapeutic applications for neurological diseases.

The takeaway

This study provides critical new insights into the molecular mechanisms controlling the blood-brain barrier, a key interface that regulates what can enter and leave the brain. Understanding these control points could lead to new ways to improve drug delivery for neurological conditions.