June 5, 2018

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It's all in your head: Brain protein targeted for alcoholism cure

University of Houston chemist Joydip Das is reporting a cure for alcoholism could be found in a protein inside the brain that plays a big role in developing tolerance to drinking. Credit: University of Houston
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University of Houston chemist Joydip Das is reporting a cure for alcoholism could be found in a protein inside the brain that plays a big role in developing tolerance to drinking. Credit: University of Houston

A protein in the brain that binds to alcohol could be the key to curing alcoholism, reports UH College of Pharmacy medicinal chemist Joydip Das in eNeuro, a journal of the Society for Neuroscience. The protein, called MUNC 13-1, plays a pivotal role in the development of tolerance to alcoholism according to Das.

"Addiction to remains one of the most significant throughout the world. A major challenge is to understand how ethanol, or alcohol, changes behavior and the brain during the descent into addiction," Das reported. Developing tolerance is a critical step in that descent.

"If a person becomes tolerant of one drink, he will have another and maybe another. If we could stop alcohol from binding into MUNC 13-1 it will help problem drinkers in reducing tolerance. If we can reduce tolerance we can reduce addiction," said Das whose study focuses on binge alcohol exposure.

The process of MUNC 13-1 binding to alcohol takes place in a brain synapse, where one nerve cell, or neuron, passes a signal to another. Specifically, the binding takes place in the presynaptic space, a much understudied portion of the synapse mechanism.

During binge alcohol exposure, alcohol creates widespread and long-lasting changes in neural activity, altering both presynaptic and postsynaptic activity.

Thus far the work has been done using the Drosophila genetic model system, which offers a simple model, but various similarities. Their activating protein is called Dunc13, the equivalent to MUNC 13-1.

"Reduction in Dunc13 produces a behavioral and physiological resistance to sedative effects of ethanol," said Das. That makes MUNC 13-1 an important target for developing drugs. "We need to develop a pill that would inhibit alcohol binding to MUNC 13 and reduce its activity. Based on our results so far, this would likely reduce the formation of , making it harder to become addicted to alcohol," said Das.

More information: Shiyu Xu et al. Ethanol Regulates Presynaptic Activity and Sedation through Presynaptic Unc13 Proteins in Drosophila, eneuro (2018). DOI: 10.1523/ENEURO.0125-18.2018

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