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‘Plumber’ protein holds key to a healthy brain

JBC paper describes anchor protein that could help with diagnosis and treatment for brain injury sufferers



forebrainNov. 29, 2012 — A protein that acts like a plumber, making sure that water is being pumped between the blood and the brain, could be the key to understanding brain damage in various diseases.

ARTICLE CAPSULE


Absence of glial alpha-dystrobrevin causes abnormalities of the blood-brain barrier and progressive brain edema 

Background: Functional blood-brain barrier requires interactions between endothelia and astrocytes but molecules involved in these contacts are not known.

Results: Absence of glial alpha-dystrobrevin protein causes leaky blood-brain barrier, water retention and progressive brain edema.

Conclusion: Glial alpha-dystrobrevin is essential for endothelium-astrocyte interactions required for blood-brain barrier functions.

Significance: Pathologies altering alpha-dystrobrevin might lead to blood-brain barrier abnormalities.

Scientists say the discovery of the anchor protein, which guards the environment in which the brain can function properly, could eventually improve diagnosis and improve treatment for sufferers of brain diseases, such as stroke, vascular dementia and brain tumours.

The function of the protein, which is one of the family of proteins that stand guard over the brain, has previously been a mystery for scientists studying the reason for brain damage that is present in some diseases.

The research team, from the University of Portsmouth School of Pharmacy and Biomedical Sciences, are also testing to see if there is less of the protein in aging brains, perhaps explaining some of the causes of brain dysfunction in older people.

The findings have been published in a November issue of The Journal of Biological Chemistry, with the researchers’ illustration being used on the Journal cover.

The blood brain barrier exists because the brain cells malfunction if they come into direct contact with blood.

Researchers found that of the known elements which make up the fully functional blood brain barrier — endothelial cells lining blood vessels, astrocytes, pericytes and neurones — astrocytes contain a specific protein called alpha-dystrobrevin, the significance of which until now had gone unnoticed.

Lead researcher Professor Darek Gorecki and his team found this protein gives astrocytes the ability to act as a plumber for the blood cells, maintaining “pumps” essential for water and ion balance between the blood circulating inside the small vessels and the brain.

If this protein is absent then an excess of water is retained, which eventually damages brain cells, causing disruption in the brain function.

Professor Gorecki said, “We knew astrocytes had an important role to play in the blood brain barrier but until now we didn’t know that this protein, found specifically in astrocytes, protects the brain from swelling and from causing it to function abnormally.”

“This finding is exciting because it helps explain cognitive deficits found in Duchenne muscular dystrophy but can also have implications for other neurological diseases, where blood brain barrier function is impaired , such as is seen in stroke, dementia, epilepsy and secondary cancers.”

Professor Gorecki and his team set out to understand how the absence of alpha-dystrobrevin affects the blood brain barrier and as a result the brain’s ability to function.

He said: “The blood brain barrier is essential for protecting the brain and creating conditions for its working but its precise structure and function is one of science’s greatest mysteries.

“Scientists still aren’t sure what it exactly consists of, how it protects the brain, how it changes in various brain diseases or how to make essential life-extending drugs pass through it.”

Professor Gorecki has spent 20 years studying the molecular pathology of Duchenne muscular dystrophy and the cognitive impairment associated with this disease. He recently won a Fulbright scholarship to research further some of these mechanisms and is recognised worldwide as a leading expert in the condition.