Prof. Joydip Das holds a frozen vial of Protein Kinase C epsilon, a human enzyme that may play a role in alcohol intoxication
This is a story about drunken mice, a tiny protein in your brain, and an alcohol researcher who doesn’t really drink much himself.
Let’s start with him. Professor Joydip Das was born in Calcutta, in the Indian state of West Bengal. Like the fierce Bengal tiger, Das is also a hunter.
But his targets are tiny, and they’re located in our brains. Das wants to ferret out the exact molecular spots where alcohol molecules go and do their intoxicating work.
“So this is a very grey area on alcohol research and we are basically trying to identify targets of alcohol in the brain.”
Despite being the most widely consumed drug in the world, alcohol is still somewhat of a scientific mystery. We know that when we drink, molecules of alcohol travel through the blood to the brain, where they somehow gum up the cognitive chemistry.
“Compared to other drugs, the targets of alcohols are not well defined.”
It’s true. Scientists actually know a lot more about the so-called targets for marijuana and heroin. They know the exact receptors in the brain where heroin molecules latch on. By docking with those receptors, heroin accelerates the normal flow of dopamine, and that creates the “high.”
But scientists are less clear about alcohol. Alcohol molecules are very small, and they migrate all over the body and into the brain. Dr. Antonio Noronha is director of neuroscience and behavior at the National Institute on Alcohol Abuse and Alcoholism.
“Now, the problem with alcohol is because it gets into just about every cell, and you know interacts with membrane proteins and lipids and gets into everything that it’s very difficult to work with, because it’s not just one target. So there are multiple targets.”
There are some drugs on the market to treat alcoholism, but they are not very effective, and they don’t work for everyone. If they want to design a better drug, scientists need to know more about all these targets. Das is focusing on a little protein inside the neuron. And it’s called…
“Protein Kinase C epsilon , or PKC epsilon.”
Got that? Protein Kinase C epsilon, or PKC epsilon for short. It’s an enzyme that shuttles phosphate around inside the cell.
A computer model of the structure of Protein Kinase C epsilon,
showing the suspected binding site targeted by alcohol
So why is Das zeroing in on PKC epsilon? That brings us to the drunken mice. Addiction scientists have conducted numerous studies with lab mice, getting them drunk and measuring the effects. Das wasn’t part of one particular experiment, but it caught his eye. The other scientists bred mice who don’t have PKC epsilon, then offered them alcohol.
“We found that if we knock out or remove the Protein Kinase C epsilon gene from a mouse, it consumes 75 percent less alcohol, so that shows a strong evidence that this protein is involved in the regulation of alcohol actions.”
In other words, if you take the PKC epsilon out of the mouse, you also take much of the desire to drink.
“And what happens when you try to get them drunk?”
“Um, they drink less. They don’t prefer to drink alcohol, and so they stay away from alcohol.”
“So they’re not very fun mice.”
“I wouldn’t want them at the party.”
All joking aside, the stakes are high. A truly effective drug for alcohol abuse could be a blockbuster. But Das cautions that he is years from even designing a drug, let alone testing it in mice or humans. PKC-epsilon appears to play a role. But how big a role is still unknown. Das plans to continue his hunt over the next three years, using the $450,000 grant from the NIAAA.
From the KUHF Health Science and Technology Desk, I’m Carrie Feibel.