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A new Johns Hopkins University study supports the
idea that high doses of cocaine can cause brain
cells to cannibalize themselves—but researchers have
also identified an experimental compound that could
be a possible antidote, able to prevent the damage.
The research team hopes that this compound, called
CGP3466B, eventually could lead to treatments that
protect adults and infants from the devastating
effects of cocaine on the brain. A summary of their
recent findings will be published online this week
in the Proceedings of the National Academy of
Sciences.
Working with mice, the Hopkins researchers
discovered that cocaine-induced brain cell death
occurs through a process called autophagy, during
which cells literally digest their own insides. They
also found signs of autophagy in the brain cells of
mice whose mothers received cocaine while pregnant.
The process of autophagy is a normal and much-needed
cellular "cleanup" that rids cells of accumulated
debris. Only when this process accelerates and spins
out of control does it cause cell death.
"A cell is like a household that is constantly
generating trash," says Prasun Guha, a postdoctoral
fellow at Johns Hopkins and lead author of the
paper. "Autophagy is the housekeeper that takes out
the trash—it's usually a good thing. But cocaine
makes the housekeeper throw away really important
things, like mitochondria, which produce energy for
the cell."
From their past studies the researchers already knew
that nitric oxide, a gas which brain cells use to
communicate, and GADPH, an enzyme, were involved in
this process. They also knew that the experimental
compound CGP3466B was proven to disrupt nitric
oxide/GAPDH interactions. So they tested the
compound to see if it could halt the cocaine-induced
autophagy.
Their results indeed confirmed that CGP3466B worked
to protect the mice's nerve cells from death by
cocaine.
The researchers are hopeful that their continued
work with CGP3466B could lead to treatments for
brain damage associated with cocaine use. But they
caution that many more years of studies, in both
mice and humans, are necessary to show definitively
whether the compound is effective for this purpose.
CGP3466B is already known to be safe for humans,
since it's been tested in past (though unsuccessful)
clinical trials to treat Parkinson's disease and ALS.
The Johns Hopkins research team had previously found
that CGP3466B was able to protect the brain cells of
live mice from the fatal effects of cocaine, but
only in this new study did they connect that
phenomenon to autophagy.
See also
Researchers Find Textbook-Altering Link Between
Brain, Immune System (2015-06-10)
Link...
Lymphatic vasculature: A cholesterol removal system
(2013-04-12)
Link...
For more information
PNAS
Cocaine elicits autophagic cytotoxicity via a nitric
oxide-GAPDH signaling cascade
Link...
Johns Hopkins University
Link...
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