Neuroprotective Protein Atlas Positions the Blood-Brain Barrier as a Selective Checkpoint
The blood-brain barrier keeps most proteins in the bloodstream out of the brain, but not all. The pathways that import them are damaged early in Alzheimer’s disease models, hinting at new ways to treat the disease. The post Neuroprotective Protein Atlas Positions the Blood-Brain Barrier as a Selective Checkpoint appeared first on GEN - Genetic Engineering and Biotechnology News .
A team of researchers has developed the first comprehensive atlas of neuroprotective proteins that successfully cross the blood-brain barrier and reach the brain, according to a study published in Cell. The discovery provides insight into the blood-brain barrier's role as a selective checkpoint, rather than merely a physical barrier.
Working with mice, scientists from the Gladstone Institutes, UC San Francisco, and other institutions created the atlas, which currently lists 92 proteins. The study suggests that the blood-brain barrier is more than a physical boundary, playing an active role in selecting and delivering protective proteins from the bloodstream to specific brain cells.
The researchers generated the atlas using a bioorthogonal proteomics strategy, tagging blood proteins and tracking their movement into the brains of mice. Of the 861 proteins they tracked, 92 successfully crossed into the brain. Most of these proteins originated in the liver, adipose tissue, or the intestine, and were directed to specific brain cells to perform specialized functions.
One key example is the liver protein apolipoprotein AI (APOA1), which, when present in the brain, activates a pathway crucial for maintaining healthy astrocyte connections. APOA1 deficiency has been linked to a higher risk of Alzheimer's disease. The study also found that the blood-brain barrier begins to fail in its protein import function even before it breaks down entirely in Alzheimer's disease.
This loss of protective proteins contributes to neuronal connection loss, early behavioral changes, and other disease symptoms. By increasing the supply of APOA1 to the brain, the team demonstrated that mice showed fewer signs of the disease. This finding suggests that Alzheimer's disease may originate from a "severed supply line" between the brain and the rest of the body, rather than starting entirely within the brain.
The researchers propose several potential treatment strategies, including boosting the production of beneficial proteins like APOA1, harnessing the brain's natural "ZIP code" system to deliver therapies directly to specific brain cells, and improving the efficiency of drug delivery through the blood-brain barrier by utilizing its transport machinery.
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