addiction

Poison Curare Could Lead To Medication To Fight Tobacco Addiction: Researchers at the Laboratory for Structural Neurobiology at K.U. Leuven have found 3-D images of protein being paralyzed by poison curare for the very first time. Curare has a paralyzing ability; the poison’s active chemical component is typically used in lung surgery. While scientists still do not known exactly how it works, 3-D images have helped scientists to get some idea of how certain medications can be helpful against muscle diseases, sleeping disorders and of course, tobacco addiction.

To lay it out, the human cell membrane can host more than 7,000 proteins; researchers have only been able to identify the assembly and purpose of 27. For communication, ion channels are an extremely important class of membrane proteins. Due to the development of The Laboratory for Structural Neurobiology at K.U. Leuven, 3-D structures have been designated in ion channels.

An explanation given by Professor Ulens, the director of The Laboratory for Structural Neurobiology, helps us to understand what this means. “We are locksmiths who examine on an atomic scale how a key — the poison — fits the lock of a door — the ion channel — and how the key keeps the door locked. Some kinds of poison only fit one lock, but curare is a passkey that can close various ion channels. Using 3D knowledge of the structure of this lock, researchers are able to develop passkey medications for a class of disorders. Or they can develop a specific medication for one disorder, such as tobacco addiction for example, as nicotine affects one specific ion channel.

Ion channels are actually switches. The proteins are shaped like microscopic pores that can open and close. Ions — charged particles — flow in or out of the cells through them. Poisons are able to disrupt the communication between cells in the body by blocking ion channels. Curare is the poison the indigenous populations of the Amazon use while hunting. They apply the poison to their arrows in order to paralyze their prey. Tubocurarine — the active chemical component of curare — paralyses the muscles and can shut down respiration, resulting in death.

The fact that so little is known about membrane proteins is related to the fatty environment of the cell membrane. In X-ray crystallography — the standard technique to study proteins — crystals of proteins are grown in water and then X-rayed in order to expose and examine their structure. Forming crystals of fatty membrane proteins is difficult, however.”

Professor Ulens goes on to explain how his team was able to evade this issue: “For the past ten years, researchers were forced to get in through the backdoor: a chemical copy of a section of ion channel. Chemically similar, but not porous. As a result, the formation of crystals was much easier. For the first time, our lab has applied the back entrance to the ion channel, which is sensitive to curare. We now have an image of how this class of ion channels recognizes chemical substances.”

In the future, Ulens expects to use the results in contribution to a development of new medications. “In the past, the pharmaceutical industry developed medications by releasing hundreds of thousands of substances into ion channels. If a certain substance caused a reaction, it would be tested on patients — a system of trial and error. Our research results in the more goal-oriented development of medications: by acquiring insight into the three-dimensional structure of an ion canal, specific medications that bind to the protein can be developed.”