A team of scientists from Johns Hopkins has published a study in the Proceedings of the National Academy of Sciences pointing to the fact that cocaine induces brain cells to consume themselves in a process known as autophagy; but the researchers also came up with a compound to counter this process.
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The study was carried out on lab mice and funded by a grant from the National Institute on Drug Abuse.
"We performed 'autopsies' to find out how cells die from high doses of cocaine," said Solomon Snyder, professor of neuroscience at the Johns Hopkins University School of Medicine. "That information gave us immediate insight into how we might use a known compound to interfere with that process and prevent the damage."
Synder and his team in 1990 found that brain cells utilize the gas nitric oxide to communicate with another, prompting him to analyze the impact of the gas on brain cells over the next 10 years. And in 2013, the researchers discovered that nitric oxide plays a part where cocaine causes brain cells to die via its interaction with GAPDH, an enzyme. But how this process plays was not immediately known.
To know how, the team evaluated nerve cells from mouse brains for a clue. Snyder revealed that cells can die from extreme temperatures, toxins, and physical trauma – just like animals; while it is also possible for cells to kill themselves via chemically programmed procedures managed by certain proteins.
"A cell is like a household that is constantly generating trash," said 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."
Since the team was aware that GAPDH and nitric oxide played a part in cells consuming themselves, they evaluated the impact of CGP3466B on the whole process because the compound is reputed to disturb the interaction between nitric oxide and GAPDH, stopping cell autophagy induced by cocaine.
The researchers eventually found that CGP3466B could save brain cells of mice from killing themselves in the presence of cocaine, even though there were yet to fully connect this event with autophagy. And when a dose of cocaine was given to mice, the researchers found autophagy in their brain cells – linked to proteins.
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"Since cocaine works exclusively to modulate autophagy versus other cell death programs, there's a better chance that we can develop new targeted therapeutics to suppress its toxicity," revealed Maged M. Harraz, a research associate at Johns Hopkins and lead co-author of the paper.