Chemical compound found in tree bark stimulates growth, survival of brain cells

Researchers have identified a compound in tree bark that mimics the chemical reactions of a naturally occurring molecule in the brain responsible for stimulating neuronal cell signaling. Neuronal cell signaling plays a crucial role in the growth, plasticity and survival of brain cells.

The tree bark compound, known as gambogic amide, behaves much like Nerve Growth Factor (NGF), a molecule found in the brain. NGF binds to TrkA, a neuronal receptor, and activates neuronal signaling. It is known that the loss of TrkA density correlates with neuronal atrophy and severe cognitive impairment such as that associated with Alzheimer's disease.

Because gambogic amide also binds to TrKA and activates neuronal signaling, the researchers believe it may have potential as a therapeutic treatment in people affected by neurodegenerative disease, such as stroke, AlzheimerÕs disease and peripheral diabetic neuropathies.

Results of the study are published online in the Proceedings of the National Academy of Sciences and will be published in a future print edition.

The research was conducted by Emory University scientists Keqiang Ye, PhD, associate professor of pathology and laboratory medicine; first author Sung-Wuk Jang, PhD, and Masashi Okada, PhD, post-doctoral fellows in Dr. Ye's lab; Iqbal Sayeed, PhD, instructor; Donald Stein, PhD, Asa G. Candler Professor of Medicine; and Peng Jin, PhD, assistant professor of human genetics; and Dr. Ge Xiao at the Centers for Disease Control and Prevention.

Gambogic amide is derived from gambogic acid, a major ingredient of gamboges, a brownish-orange resin exuded from the Southeast Asian Garcinia hanburryi tree. The resin has been used in that area of the world for thousands of years to treat cancers without any reported toxicity to noncancerous cells.

"Humans actually have a naturally occurring molecule in the body, Nerve Growth Factor (NGF), which stimulates the growth and differentiation of certain types of nerve cells. However, NGF has poor pharmocokinetics and bioavailability when synthetically manufactured and used therapeutically, and it is also expensive to produce," Dr. Ye says.

"Previous research had focused on copying the chemical structure of NGF, but the cyclopeptide mimetics are not potent enough to use as a therapeutic agent. Instead, we decided that we needed to identify a more robust molecule that would pharmacologically mimic NGF's effect on brain cells by binding to TrkA. What we came up with was gambogic amide." Dr. Ye says.

The researchers are now conducting further pre-clinical research to investigate how the body processes gambogic amide and to confirm that it is in fact non-toxic.

Source: Emory University

Related stories:

New approach to gene therapy may shrink brain tumors, prevent their spread
Massachusetts General Hospital (MGH) researchers are investigating a new approach to gene therapy for brain tumors – delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading. An animal study published in the journal Molecular Therapy, the first to test the feasibility of such an approach, found that inducing mouse brain cells to secrete human interferon-beta suppressed and eliminated growth of human glioblastoma cells implanted nearby.
Rare genetic disorder gives clues to autism, epilepsy, mental retardation
A rare genetic disorder called tuberous sclerosis complex (TSC) is yielding insight into a possible cause of some neurodevelopmental disorders: structural abnormalities in neurons, or brain cells. Researchers in the F.M. Kirby Neurobiology Center at Children's Hospital Boston, led by Mustafa Sahin, MD, PhD, and Xi He, PhD, also found that normal neuronal structure can potentially be restored.
Cocaine addiction linked to voluntary drug use and cellular memory
Rats that voluntarily use cocaine show a persistent cellular memory in the brain's reward center even after several months of abstinence from the drug, while their involuntary counterparts had no such memory, according to a new study by researchers at the University of California, San Francisco.
MicroRNA implicated as molecular factor in alcohol tolerance
In recent years, a class of small molecules known as microRNA have been found to play an important role in regulating gene products in most animal and plant species. A new study now indicates that microRNA may influence the development of alcohol tolerance, a hallmark of alcohol abuse and dependence. Researchers supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) report the findings in the July 31 issue of the journal Neuron.
'Intrabody' can mop up mutant protein in Huntington's disease model
Scientists have created a tool for mopping up the clumps of mutant protein that drive neurodegeneration in Huntington's disease. Emory University researchers engineered a virus to make an intracellular antibody or "intrabody" against huntingtin, the protein whose mutant forms poison the brain cells of people with Huntington's.
Imaging study provides glimpse of alcohol's effect on brain
New brain imaging research published this week shows that, after consuming alcohol, social drinkers had decreased sensitivity in brain regions involved in detecting threats, and increased activity in brain regions involved in reward. The study, in the April 30 issue of The Journal of Neuroscience, is the first human brain imaging study of alcohol’s effect on the response of neuronal circuits to threatening stimuli.
Study suggests antibiotic may prevent dreaded brain fever
Two researchers from National Brain Research Center (NBRC) suggest that a common antibiotic called minocycline may prevent children from death due to Japanese encephalitis (JE), or commonly known as brain fever. Japanese Encephalitis virus is the causative agent for JE. Although there is no consolidated official figure for JE cases in India, a rough estimate would indicate a few thousands fatalities every year.
Imaging study reveals rapid formation of Alzheimer's-associated plaques
The amyloid plaques found in the brains of Alzheimer’s disease patients may form much more rapidly than previously expected. Using an advanced microscopic imaging technique to examine brain tissue in mouse models of the devastating neurological disorder, researchers from the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), working with colleagues from Washington University School of Medicine, find that plaques can develop in as little as a day and that Alzheimer’s-associated neuronal changes appear soon afterwards. Their report will appear in the Feb. 7 issue of Nature.

News discussion:

Medicine & Health news