A new study found that high doses of cocaine lead to quite a morbid process: brain cells are triggered to cannibalize themselves.
Researchers from Johns Hopkins University School of Medicine found that cocaine initiates a process called autophagy, a cleanup mechanism that rids cells of debris. While the process is normal, it becomes harmful with high doses of cocaine as the substance triggers it to go haywire. The mixed-up process eventually prompts the cells to eat themselves and die.
"A cell is like a household that is constantly generating trash," says lead author Prasun Guha, adding that the process is actually a good thing, but then cocaine pushes it to throw even the valuable stuff, such as energy-generating mitochondria.
To perform their study, the researchers studied the nerve cells of mouse brains. They particularly looked into the proteins that control and chemically program cells to die. When they identified the changes in protein levels in the models, they found that cocaine truly induces brain cell death via uncontrolled autophagy.
The recent findings confirmed earlier studies on cocaine-induced autophagy. In 2013, the team first discovered that an enzyme called GAPDH plays a role in cocaine-induced cell death when combined with nitric oxide.
With this in mind, the researchers then tested the ability of a compound called CGP3466B to counter ucontrolled autophagy. The compound is said to impair interaction between nitric oxide and GAPDH. The researchers found that CGP3466B exhibited brain cell-protective abilities against autophagy caused by cocaine.
"We performed 'autopsies' to find out how cells die from high doses of cocaine," says co-author Solomon Snyder. The data they collated instantly gave them an idea of how they might use CGP3466B to halt the process and prevent damage.
In the future, the research team hopes to lead studies that are aimed towards finding treatments against cocaine-induced brain defects.
CGP3466B has been tested safe for humans as it is already being used for Parkinson's treatment. However, the authors says more studies are needed to prove its effectiveness against the negative effects of cocaine. They also want to test other derivatives of the enzyme to find out if it kills other cells outside the brain.
The study was featured in the Proceedings of National Academy.
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