The MUNC 13-1 protein appears to play an important role in the development of tolerance to alcoholism. The research comes from UH College of Pharmacy, based on research undertaken by medicinal chemist Dr. Joydip Das. This is based on research using the humble fruit fly.
According to Dr. Das, the work is potentially of great importance: “Addiction to alcohol remains one of the most significant mental health problems throughout the world. A major challenge is to understand how ethanol, or alcohol, changes behavior and the brain during the descent into addiction.”
Particularly with binge alcohol exposure, consumption of alcohol leads to long-lasting changes in neural activity. These alter presynaptic and postsynaptic activity. With this process, MUNC 13-1 binds to alcohol and this takes place in a brain synapse. Here a nerve cell passes a signal to another. The binding step takes place in the presynaptic space. This is a generally understudied area of the synapse mechanism.
A route into alcoholism is developing tolerance, and this is the basis of Dr. Das’ research. The academic goes on to explain: “If a person becomes tolerant of one drink, he [sic] 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.”
Therefore, a reduction in the protein should lead to behavioral and physiological resistance to sedative effects of ethanol. The medical possibility is to develop a pill that will prevent alcohol binding to MUNC 13 and thus reduce the activity levels. This would mean, for the patient, that it would become far more difficult to become addicted to alcohol.
Importantly the research is at an early stage, with research conducted on the fly Drosophila, using a genetic model system. Considerably more research is required before trials are conducted humans.
The research why the fruit fly has been used is because they have an activating protein is called Dunc13, which functions in a similar way to MUNC 13-1. Here data indicates that ethanol targets the active zone in reducing synaptic vesicle exocytosis.
The research has been published in the journal eNeuro, which is a journal of the Society for Neuroscience. The research paper is titled “Ethanol Regulates Presynaptic Activity and Sedation through Presynaptic Unc13 Proteins in Drosophila.”
