New Proteomic Mapping of the Blood-Brain Barrier Reveals Molecular Targets for Drug Delivery and Neurodegeneration

Researchers at HHMI’s Janelia Research Campus identify SLC7A1 and HYAL2 as key proteins that regulate the permeability of the brain's protective barrier.

By: AXL Media

Published: Apr 10, 2026, 8:20 AM EDT

Source: Information for this report was sourced from EurekAlert!

Decoding the Brain's Biological Security System

The blood-brain barrier acts as a highly selective gatekeeper, determining which substances can transition from the circulatory system into the brain's delicate environment. While this barrier is essential for protection, it frequently obstructs the delivery of vital medications for neurological conditions. A team led by Jiefu Li, a group leader at HHMI’s Janelia Research Campus, has developed a revolutionary method to examine the proteins lining the luminal surface of these blood vessels. By illuminating this internal interface, the researchers hope to understand how the brain’s "bouncer" chooses which molecules pass and which are barred from entry.

Mapping the Luminal Surface Proteome

The researchers focused on the luminal surface, the internal lining of blood vessels that serves as the direct interface between circulating blood and organ tissue. To understand the function of this specialized part of the vascular system, the team created an easy-to-use labeling technique to identify all proteins present on this surface. This approach allows scientists to observe how the molecular composition of the blood-brain barrier changes over time. According to Li, identifying these molecular players is critical for understanding how the vasculature system adapts its functions across different organs and developmental stages.

Evolution of the Barrier from Infancy to Old Age

In a collaborative effort with the Broad Institute’s Proteomics Platform, the researchers mapped the brain's vascular proteins through development, adulthood, and senescence. The findings revealed that as the brain matures, there is a marked decrease in proteins responsible for building new vessels and transporting molecules. Conversely, as the brain ages, the vascular network becomes increasingly stiff and less adaptable due to shifting protein profiles. These changes provide a biological explanation for why the brain becomes more vulnerable to certain diseases as an organism grows older.