(Press-News.org) Contact information: Jerry Barach
jerryb@savion.huji.ac.il
972-258-82904
The Hebrew University of Jerusalem
Neurotransmitters resarch can promote better drugs for brain disorders
Hebrew University scientists decipher mechanism
Jerusalem, January 7, 2014 -- Although drugs have been developed that inhibit the imbalance of neurotransmitters in the brain – a condition which causes many brain disorders and nervous system diseases – the exact understanding of the mechanism by which these drugs work has not yet been fully explained.
Now, researchers at the Hebrew University of Jerusalem, using baker's yeast as a model, have deciphered the mode by which the inhibitors affect the neurological transmission process and have even been able 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 of the basic tasks of our existence are executed by the brain – whether it is breathing, heartbeat, memory building or physical movements – which depend on the highly regulated and efficient release of neurotransmitters – chemicals that act as messengers enabling extremely rapid connections between the neurons in the brain.
When even one part of the everyday "conversation" between neighboring 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. Tetrabenazine has long been used for the treatment of motor dysfunctions associated with Huntington's disease and other movement disorders. However, the mechanism by which the drug affects the storage of neurotransmitters was not fully understood.
The Hebrew University study set out, therefore, to achieve an understanding of the basic biochemical mechanism underlying the VMAT reaction, with a view towards better controlling it through new drug designs.
The research was conducted by in the laboratory of Prof. Shimon Schuldiner of the Hebrew University's Department of Biological Chemistry; Dr.Yelena Ugolev, postdoctoral fellow in the laboratory; and research students Tali Segal, Dana Yaffe and Yael Gros.
To identify protein sequences responsible for tetrabenazine binding, the Hebrew University scientists harnessed the power of yeast genetics along with the method of directed evolution.
Expressing the human protein VMAT in baker's yeast cells confers them with the ability to grow in the presence of toxic substrates, such as neurotoxin MPP+. Directed evolution mimics natural evolution in the laboratory and is a method used in protein engineering.
By using rounds of random mutations targeted to the gene encoding the protein of interest, the proteins can be tuned to acquire new properties or to adapt to new functions or environment.
The study 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.
Utilizing these new, controllable adaptations could serve as a guide for clinical scientists to develop more efficient drugs for brain disorders associated with neurotransmitter imbalance, say the Hebrew University researchers.
INFORMATION:
Neurotransmitters resarch can promote better drugs for brain disorders
Hebrew University scientists decipher mechanism
2014-01-07
ELSE PRESS RELEASES FROM THIS DATE:
The 5 fingers of our feathered friends: New research results on the evolution of bird wings
2014-01-07
The 5 fingers of our feathered friends: New research results on the evolution of bird wings
In most tetrapods (land vertebrates) the fourth (ring) finger is the first to develop in the embryo. And in birds, the finger on the outside of the hand (posterior, ...
Gemini Planet Imager first light
2014-01-07
Gemini Planet Imager first light
World's most powerful exoplanet camera turns its eye to the sky
This news release is available in Spanish.
After nearly a decade of development, construction, and testing, the world's most advanced instrument for directly imaging ...
To keep their eye on the ball, batters mostly use their heads
2014-01-07
To keep their eye on the ball, batters mostly use their heads
How do hitters track pitches in baseball? Study in optometry and vision science gives new insights
Philadelphia, Pa. (January 7, 2014) - Baseball players at bat follow coaches' advice to "keep ...
New algorithm can dramatically streamline solutions to the 'max flow' problem
2014-01-07
New algorithm can dramatically streamline solutions to the 'max flow' problem
Research could boost the efficiency even of huge networks like the Internet
Finding the most efficient way to transport items across a network like the U.S. highway system or the ...
When germs attack: A lens into the molecular dance
2014-01-07
When germs attack: A lens into the molecular dance
Researchers at Johns Hopkins have zoomed in on what is going on at the molecular level when the body recognizes and defends against an attack of pathogens, and the findings, they say, could influence how drugs are ...
Synthetic genetic clock checks the thermometer
2014-01-07
Synthetic genetic clock checks the thermometer
Rice University leads study to counter effects of temperature on synthetic gene circuits
HOUSTON – (Jan. 7, 2014) – Genetic systems run like clockwork, attuned to temperature, time of day and many other factors as they regulate ...
Dabrafenib in melanoma: Added benefit not proven
2014-01-07
Dabrafenib in melanoma: Added benefit not proven
No differences could be shown for mortality, symptoms and quality of life / concerning side effects, data too uncertain
Dabrafenib (trade name: Tafinlar) has been approved in Germany ...
Aflibercept in macular oedema: Added benefit not proven
2014-01-07
Aflibercept in macular oedema: Added benefit not proven
Neither the new drug nor the comparator therapy was used in accordance with their approvals in the studies
For the third time in one year, the German Institute for Quality ...
Increased risk of prostate cancer in African American men; implications for PSA screening
2014-01-07
Increased risk of prostate cancer in African American men; implications for PSA screening
New Rochelle, NY, January 7, 2014—African American men have an increased risk of prostate cancer and are two times more likely than Caucasian American ...
Sugar-burning in the adult human brain is associated with continued growth, and remodeling
2014-01-07
Sugar-burning in the adult human brain is associated with continued growth, and remodeling
Research published in the journal Cell Metabolism shows that hotspots of fuel consumption in the adult brain also show key characteristics of developing brain regions
SEATTLE, ...
LAST 30 PRESS RELEASES:
From octopus intelligence to smart artificial blood vessels: 2025 Schmidt Science Fellows to break new ground with interdisciplinary research
Experts challenge aspirin guidelines based on their undue reliance on a flawed trial
McGill discovery sheds new light on autism, intellectual disabilities
Cellular changes occur even below the hexavalent chromium limit
Study suggests a new way to curb social media’s body image toll
Plant doctor: An AI system that watches over urban trees without touching a leaf
Study tracks chromium chemistry in irradiated molten salts
Scientists: the beautiful game is a silver bullet for global health
Being physically active, even just a couple of days a week, may be key to better health
High-fat diet promote breast cancer metastasis in animal models
A router for photons
Nurses and AI collaborate to save lives, reduce hospital stays
Multi-resistance in bacteria predicted by AI model
Tinker Tots: A citizen science project to explore ethical dilemmas in embryo selection
Sensing sickness
Cost to build multifamily housing in California more than twice as high as in Texas
Program takes aim at drinking, unsafe sex, and sexual assault on college campuses
Inability to pay for healthcare reaches record high in U.S.
Science ‘storytelling’ urgently needed amid climate and biodiversity crisis
KAIST Develops Retinal Therapy to Restore Lost Vision
Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response
Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid
Low LDL cholesterol levels linked to reduced risk of dementia
Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients
Almost one in ten people surveyed report having been harmed by the NHS in the last three years
Enhancing light control with complex frequency excitations
New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients
New insight into factors associated with a common disease among dogs and humans
Illuminating single atoms for sustainable propylene production
New study finds Rocky Mountain snow contamination
[Press-News.org] Neurotransmitters resarch can promote better drugs for brain disordersHebrew University scientists decipher mechanism