Researchers at Johns Hopkins have discovered that the
same ingredient used in dandruff shampoos to fight the
burning, itching and flaking on your head also can calm
overexcited nerve cells inside your head, making it a
potential treatment for seizures. Results of the study can
be found online in Nature Chemical Biology.
Epilepsy and other seizure disorders result when
nerves excessively or inappropriately "fire" in the brain.
The brain's "off" switches fail in part due to protein
defects that prevent potassium from exiting nerve cells and
calming them. "Channels that carry potassium must open on
cue to make sure nerve cells only fire for defined periods
of time," said Min Li, professor of
neuroscience at Johns Hopkins.
In their studies of these channels, Li and his
colleagues developed a new way of testing thousands of
druglike molecules to find any that could turn the
potassium switch on or off. Their approach involved
chemically shaving off all the potassium channels on the
cell surface and forcing the cells to make new channels. By
measuring the activity of the new channels, the researchers
could identify molecules that accelerated the recovery.
One chemical that proved quite effective in improving
channel recovery was zinc pyrithione, or ZnPy, the active
ingredient in many dandruff shampoos. Li explains that ZnPy
has a shape that allows it to fit into the gate region of
the channel protein and allow more potassium flow.
"If you think of these channels as doors on the cell's
surface," Li said, "then ZnPy made this door both easier to
open and stay open longer. It's like a tunable hinge that
helps sticky doors swing freely."
The researchers then tested defective channels that
contain the same mutations known in humans to cause mild
epilepsy-like seizures in infants. Bathing cells with small
amounts of ZnPy caused the mutant potassium channels to let
three times as much potassium flow through, raising the
possibility of restoring normal nerve cell activity.
"Most drug discoveries uncover chemicals that stop
things from working; it's a lot easier to close or block a
door than open it," Li said. "But here we found a chemical
that makes a defective protein work better. So now we have
a chance to actually try to fix the causes of epilepsy
rather than traditionally circumventing them. Plus, this
study really shows that we don't fully appreciate the
biological roles of many familiar chemicals that surround
us."
The research was funded by the National Institutes of
Health. Authors on the paper are Qiaojie Xiong, Haiyan Sun
and Li, all of Johns Hopkins.