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Body Language
Summer 2014

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systems biology

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micrograph showing gene-deficient capillaries leaking dye, an indication of the gene's role in permeability
  

Like a bouncer at an exclusive nightclub, the blood-brain barrier allows only select molecules to pass from the bloodstream into the fluid bathing the brain. Nutrients get in; toxins and pathogens don’t. The barrier also ensures that waste products are filtered out of the brain and whisked away.

Although the barrier helps maintain the delicate environment necessary to the human brain’s health, there is a problem: the barrier is so discerning, it won’t let medicines in. Researchers haven’t been able to coax it open, either; they don’t yet know enough about how the barrier forms or how it functions.

Now, an HMS team has identified a gene in mice, Mfsd2a, which may be responsible for limiting the barrier’s permeability, and has found that the molecule it produces, Mfsd2a, works in an unexpected way. Their study was published online May 14 in Nature.

Most attempts to understand and manipulate blood-brain barrier function have focused on tight junctions that prevent all but a few substances from squeezing between barrier cells. Chenghua Gu, an HMS associate professor of neurobiology, and her research team discovered that Mfsd2a appears to affect transcytosis, a little-studied process in which substances travel through the barrier cells in bubbles called vesicles. Transcytosis occurs frequently at other sites in the body but is normally suppressed at the blood-brain barrier. Mfsd2a may be one of the suppressor agents.

“It’s exciting. This is the first molecule identified that inhibits transcytosis,” says Gu. “It opens up a new way of thinking about how to design strategies to deliver drugs to the central nervous system.”

Mfsd2a has a human equivalent, so controlled blocks to its activity could allow the passage of drugs that treat life-threatening conditions in humans such as brain tumors and infections.

Conversely, because researchers have begun to link blood-brain barrier degradation to several brain diseases, boosting Mfsd2a or the molecule it produces might help strengthen the barrier and perhaps alleviate diseases such as Alzheimer’s, multiple sclerosis, and amyotrophic lateral sclerosis. The findings may also have implications for other areas of the body that rely on transcytosis, such as the retina and kidney.

Image: Gu lab

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Issue

Body Language
Summer 2014

Topics

systems biology

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