Health scan: Work on neurotransmitters could improve drug design for brain disorders

Although there are drugs to inhibit the imbalance of neurotransmitters in the brain, exact understanding of the mechanism by which these drugs work has not yet been fully understood.

By JUDY SIEGEL-ITZKOVICH
Brain (photo credit: Wikicommons)
Brain
(photo credit: Wikicommons)
Although there are drugs to inhibit the imbalance of neurotransmitters in the brain – a condition that causes many brain disorders and nervous system diseases – the exact understanding of the mechanism by which these drugs work has not yet been fully understood.
Using baker’s yeast as a model, researchers at the Hebrew University of Jerusalem, have deciphered the mode by which the inhibitors affect the neurological transmission process and have been able even to manipulate it. Their work, reported in a recent article in the Journal of Biological Chemistry, raises hopes that these insights could eventually guide clinical scientists to develop new and more effective drugs for brain disorders associated with neurotransmitter imbalance.
All basic tasks of human beings – breathing, heartbeat, memory building or physical movements – are executed by the brain. They depend on the highly regulated and efficient release of neurotransmitters – chemicals that act as messengers enabling extremely speedy connections between the neurons in the brain.
When even one part of the everyday “conversation” between adjacent neurons breaks down, the results can be devastating. Many brain disorders and nervous system diseases, including Huntington’s disease, various motor dysfunctions and even Parkinson’s disease, have been linked to problems with neurotransmitter transport. The neurotransmitters are stored in the neuron in small, bubble-like compartments, called vesicles, containing transport proteins that are responsible for the storage of the neurotransmitters into the vesicles.
The storage of certain neurotransmitters is controlled by what is called the vesicular monoamine transporter (VMAT), which is known to transport a variety of vital neurotransmitters, such as adrenaline, dopamine and serotonin. In addition, it can also transport the detrimental MPP+, a neurotoxin involved in models of Parkinson’s disease. A number of studies demonstrated the significance of VMAT as a target for drug therapy in a variety of pathologic states, such as high blood pressure, hyperkinetic movement disorders and Tourette syndrome.
Many of the drugs that target VMAT act as inhibitors, including the classical VMAT2 inhibitor, tetrabenazine, which has long been used for the treatment of motor dysfunctions in Huntington’s disease and other movement disorders. But the mechanism by which the drug affects the storage of neurotransmitters was not fully understood.
To identify protein sequences responsible for tetrabenazine binding, the Jerusalem scientists harnessed the power of yeast genetics along with the method of directed evolution. Their work led to identification of important flexible domains (or regions) in the structure of the VMAT, responsible for producing optional rearrangements in tetrabenazine binding, and also enabling regulation of the velocity of the neurotransmitter transporter. The researchers believe their work could lead to the development of more efficient drugs for brain disorders that involve neurotransmitter imbalance.
TESTING WITH PAINLESS TEARS Babies sometimes have to be testing for vitamin deficiencies – always by taking a blood sample, which is momentarily painful for the infant and no less painful for parents who hold them. But now, scientists at Michigan Technological University are working on a painless alternative.
Instead of using blood plasma, chemical engineering Prof. Adrienne Minerick is developing a simple analysis tool using tears but without really crying. Just place a simple absorbent strip placed against the lower eyelid to collects all the fluid needed. Ultimately, her team aims to measure levels of vitamins A, C, D, E and K, plus all the B vitamins, using tears and a hand-held diagnostic tool called a lab-on-a-chip.
During their initial work, the scientists identified all vitamins except one in baby tears using conventional lab techniques. They are comparing those measurements with vitamin levels in the babies’ blood plasma to see if they correlate; initial results are promising.
“Ideally, infants would never experience nutritional deficiencies, but there are regions of the world where up to 40 percent of children are malnourished. By the time symptoms of deficiencies are recognizable, damage has already occurred that can impact child development,” said graduate student Maryam Khaksari.
“Our easy, painless, and inexpensive method will be able to identify deficiencies much early than symptoms diagnosis, before lasting damage occurs.”
HYPNOSIS RELIEVES FATIGUE IN CANCER PATIENTS Breast cancer patients receiving radiotherapy suffer from less fatigue as a result of cognitive behavioral therapy plus hypnosis (CBTH), according to a study recently published in the Journal of Clinical Oncology.
The study, led by Dr. Guy Montgomery of the integrative behavioral medicine program at the Mount Sinai Medical School in New York City, tested 200 patients showed that the treatment group had significantly less fatigue than a control group both during treatment and for up to six months afterwards.
The average patient in a treatment group had less fatigue than 79 percent of patients in a control group at the end of radiotherapy. Six months after the end of radiotherapy, the average patient in a treatment group had less fatigue than 95% of patients in a control group. “These results support CBTH as an evidence- based complementary intervention to control fatigue in patients undergoing radiotherapy for breast cancer,” said Montgomery. “CBTH works to reduce fatigue for patients who have few other treatment options. It is also noninvasive, has no adverse side-effects, and its beneficial effects persist long after the last intervention.”