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posted by janrinok on Sunday March 09, @07:18PM   Printer-friendly

https://www.nature.com/articles/d41586-025-00554-w

A slimy barrier lining the brain's blood vessels could hold the key to shielding the organ from the harmful effects of ageing, according to a study in mice.

The study showed that this oozy barrier deteriorates with time, potentially allowing harmful molecules into brain tissue and sparking inflammatory responses. Gene therapy to restore the barrier reduced inflammation in the brain and improved learning and memory in aged mice. The work was published today in Nature1.

The finding shines a spotlight on a cast of poorly understood molecules called mucins that coat the interior of blood vessels throughout the body and give mucus its slippery texture, says Carolyn Bertozzi, a Nobel-prizewinning chemist at Stanford University in California and a lead author of the study. "Mucins play a lot of interesting roles in the body," she says. "But until recently, we didn't have the tools to study them. They were invisible."

Mucins are large proteins decorated with carbohydrates that form linkages with one another, creating a water-laden, gel-like substance. They are crucial constituents of the blood–brain barrier, a system that restricts the movement of some molecules from the blood into the brain.

Researchers have long sought ways to sneak medicines past this barrier to treat diseases of the brain. Previous work also showed that the integrity of the barrier erodes with age2, suggesting that it could be an important target for therapies to combat diseases associated with ageing, such as Alzheimer's disease.

But scientists knew little about the contribution of mucins to these changes, until Sophia Shi, a graduate student at Stanford, decided to focus on a mucin-rich layer called the glycocalyx, which lines blood vessels. Shi and her colleagues looked at what happens to the glycocalyx in the brain as mice age. "The mucins on the young blood vessels were thick and juicy and plump," says Bertozzi. "In the old mice, they were thin and lame and patchy."

[Ed's Note: Unable to access the full article. If you have full access please leave a link in the comments.--JR]

Journal Reference:
Ledford, Heidi. 'Slime' keeps the brain safe ― and could guard against ageing, (DOI: 10.1038/d41586-025-00554-w)


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  • (Score: 2, Informative) by shrewdsheep on Tuesday March 11, @08:14AM (1 child)

    by shrewdsheep (5215) on Tuesday March 11, @08:14AM (#1395977)

    https://doi.org/10.1038/d41586-025-00554-w [doi.org] ;-)

    The team went on to find that mucins in a particular class were less abundant in old mice than in young mice. The scientists also showed that a decrease in the activity of enzymes needed to produce these mucins caused the blood–brain barrier to become leakier.

    And bolstering the activity of those enzymes in old mice reduced the leakage and improved the animals’ performance on learning and memory tests. Old mice can be forgetful, says Bertozzi. “They can’t get out of the maze like they used to. But they do better on those tests after we restore the mucin barrier.”
    Sieve in the brain

    The work opens a fresh avenue of study for researchers who are exploring the blood–brain barrier, says Michelle Erickson, who studies neurobiology and physiology at the University of Washington in Seattle. “This is going to advance the field quite a bit,” she says.

    Others are interested in exploring possible age-related changes in the glycocalyx of blood vessels running through other organs. “Ageing is a concept that applies not only to the brain,” says Hideshi Okada, an emergency physician who studies vascular disorders at Gifu University Hospital in Japan. In particular, Okada wants to explore this possibility in the kidneys, because of their role in filtering the blood and because kidney function also declines with age.

    The next big question is why mucins are so important for the blood–brain barrier, says Erickson. They could function as a physical sieve, preventing certain molecules from passing through the blood-vessel walls. But Bertozzi says the proteins could also have a more complex role ― one that might reveal ways to smuggle medicines across the blood–brain barrier.

    “I have a hunch that the mucins are actually actively shuttling some things or excluding others,” she says. “We have to get to the bottom of that.”

    That's all folks. (2nd half, continuing TFS).

    Real meat: https://www.nature.com/articles/s41586-025-08589-9 [nature.com]

    • (Score: 2) by janrinok on Tuesday March 11, @08:35AM

      by janrinok (52) Subscriber Badge on Tuesday March 11, @08:35AM (#1395978) Journal

      Thank you. I'm still not able to access the full article but you have filled in the missing parts.

      --
      I am not interested in knowing who people are or where they live. My interest starts and stops at our servers.
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