X-Message-Number: 13077
From: Eugene Leitl <>
Date: Mon, 10 Jan 2000 12:45:57 -0800 (PST)
Subject: UM researchers discover 'key' to blood-brain barrier 

http://www.eurekalert.org/releases/ummc-umr010300.html

Contact: Tim Parsons

410-328-9260
University of Maryland Medical Center 

UM researchers discover 'key' to blood-brain barrier

Findings Could Lead to New Treatments for Brain Disorders

Researchers at the University of Maryland School of Medicine in
Baltimore have identified a receptor in the human brain that regulates
the interface between the bloodstream and the brain, which is known as
the blood-brain barrier. This breakthrough could lead to a better
understanding of this nearly impenetrable barrier and to treatment of
diseases that affect the brain, such as Multiple Sclerosis, brain
tumors, meningitis, Alzheimer's disease, and HIV infection. The
findings are published in the January issue of the Journal of
Neurochemistry.

The blood-brain barrier is a collection of cells that press together
to block many substances from entering the brain, while allowing
others to pass. For years, scientists knew little about how this
barrier was regulated or why certain diseases are able to manipulate
the barrier and infect the brain. Earlier research conducted at the
University of Maryland School of Medicine found that two proteins,
known as zonulin and zot, unlock the cell barrier in the
intestine. The proteins attach themselves to receptors in the
intestine to open the junctions between the cells and allow substances
to be absorbed. The new research indicates that zonulin and zot also
react with similar receptors in the brain.

"The blood-brain barrier is like a gateway to the brain. It is almost
always locked, keeping out many diseases. Unfortunately, it also keeps
out medications as well. Almost nothing can pass," explains lead
author Alessio Fasano, M.D., professor of pediatrics and physiology at
the University of Maryland School of Medicine, and director of
Pediatric Gastroenterology at the University of Maryland Hospital for
Children. "First we discovered the key, and now we've found the lock
that fits that key to open the gateway into the brain. This discovery
could help us open that gateway," explains Dr. Fasano.

Dr. Fasano and his team studied brain tissue samples obtained from a
brain and tissue bank at the University of Maryland. The brain tissue
was treated with purified zonulin and zot proteins, then examined
under a microscope. Researchers observed the zonulin and zot proteins
binding with the brain tissue. Next, they compared the results to
tests on tissue samples from the intestines.

"We've known about the blood-brain barrier for more than 100 years,
but we've never been able to figure out how it worked.  Now we have a
new piece to the puzzle," says Dr. Fasano.

"The identification of these proteins in the human brain holds the
promise of allowing us to deliver new types of medications across the
blood-brain barrier. It would be a boon to humanity if the blood-brain
barrier could be opened briefly, and safely, to allow passage of a new
generation of drugs into the brain," says Ronald Zielke, Ph.D. co-
author, professor of pediatrics and director of the brain and tissue
bank at the University of Maryland School of Medicine.

Dr. Fasano adds that more research is needed to understand how zonulin
and zot work during the formation and development of the brain. The
current study was funded by a grant from the National Institutes of
Health.

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