Agrin: Protein's Potential As A Regulator Of Brain Activity Discovered

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Protein's Potential As A Regulator Of Brain Activity Discovered

http://www.medicalnewstoday.com/medicalnews.php?newsid=42033

UC Irvine researchers have found that a protein best known for

building connections between nerve cells and muscle also plays a role

in controlling brain cell activity. The finding points to possible

therapeutic applications in the development of new drugs for

treatment of epilepsy and neurodegenerative disorders.

, professor of anatomy and neurobiology in the School of

Medicine, and his UCI colleagues discovered that agrin -- a protein

that directs synapse formation between nerve and muscle cells -- can

also inhibit the function of " pumps " that control sodium and

potassium levels within cells.

These pumps, called sodium-potassium ATPases -- or sodium pumps, for

short -- are especially important in electrically excitable cells,

where they provide the basis for electrical impulses, known as action

potentials, which are responsible for muscle contraction and

signaling between nerve cells in the brain. They do this by pumping

sodium out of a cell and pumping potassium in, setting up an

electrochemical gradient -- in a sense, turning the cell into a

battery.

If this activity isn't properly moderated, uncontrollable electrical

impulses can be triggered, which is one of the cellular mechanisms

behind an epileptic seizure, for instance.

This is where agrin comes into action. The UCI researchers observed

in laboratory tests that agrin controls the excitability of nerve

cells in the brain by regulating sodium pump activity. Adding agrin

caused nerve cells to fire electrical impulses uncontrollably. In

turn, the researchers found that they could block these electrical

impulses by introducing small fragments of agrin, which prevented the

full agrin proteins from binding their sites on the sodium pump

molecules and initiating action potentials.

" The ability of agrin to modulate nerve cell excitability suggests

that the agrin-sodium pump interactions can be exploited as a novel

therapeutic target for epilepsy and other brain disorders, "

said.

Agrin proteins are also expressed in heart tissue, and notes

that sodium pump inhibitors, such as digoxin, are commonly used to

treat congestive heart failure. Agrin may, therefore, have

therapeutic value for the treatment of diseases affecting tissues and

organs outside of the brain.