Findings May Present New Way to Stop Nicotine Cravings

Researchers were able to crystalize a protein that plays a role in nicotine addiction, which may provide a new treatment target to end tobacco cravings and treat multiple diseases, including Alzheimer's disease.

Researchers were able to crystalize a protein that plays a role in nicotine addiction, which may provide a new treatment target to end tobacco cravings and treat multiple diseases, including Alzheimer’s disease.

This breakthrough comes after years of being unable to determine the structure of the protein. It is expected that researchers will be able to better understand nicotine’s molecular effects from the recent crystallization of the protein, according to a study published by

Nature.

“It's going to require a huge team of people and a pharmaceutical company to study the protein and develop the drugs, but I think this is the first major stepping stone to making that happen," said co-author Ryan Hibbs, PhD.

The alpha-4-beta-2 nicotinic receptor protein is located on nerve cells in the brain. Nicotine binds to this receptor when someone intakes nicotine and opens a path for ions to enter the cell.

This process results in increased memory and focus, but is highly addictive. Before the current study, it was not known how nicotine is able to cause these effects.

Researchers expect that the newly crystallized 3D structures will be able to provide understanding about how nicotine is able to influence the receptor, according to the study. These findings can lead to medication that mimics its abilities.

These findings may also present treatment options for conditions such as epilepsy, mental illness, and

Alzheimer’s disease

, since they are all associated with this receptor.

Other studies have shown that smoking cessation drugs and other methods have mixed results, and are not always successful. New treatments that target the nicotinic receptor may present successful alternatives.

The researchers started attempting to determine the structure of the receptor as early as 2012, and were motivated by the high mortality rate associated with tobacco use.

Previous researchers attempted this with an electric organ of a torpedo ray, which is a rich source of nicotinic receptors and can provide biochemical information, according to the study.

“But they were never able to get the torpedo protein to crystalize,” Dr Hibbs said. “Many very good research groups had tried to do this and failed. We took a different approach.”

The previous researchers were unable to elicit the desired outcomes because the protein from the ray was unstable and unable to be genetically modified. The current researchers created a new method of mass producing the receptors through a viral infection of a human cell line, according to the study.

The infected cells then produced significant amounts of the receptors.

The newly created receptors were purified to remove the cell membrane and any other proteins. Then, the researchers mixed the receptors with chemicals that promote crystallization.

The researchers examined thousands of chemical combinations prior to growing the crystals that were bound by nicotine, and 0.2 mm long X-ray diffraction was used to capture the structure of the receptor.

Their next steps include determining the structures without the presence of nicotine, and in the presence of other molecules. Comparing the structures will allow the researchers to understand what nicotine does, and how it is different than other chemicals.

They believe that the receptor is extremely important for the treatment of various diseases, as well as nicotine cravings, and that their findings can lead to treatment options.