[ Sitemap ] [ Contact ] [ Imprint ] [ News in German ]   


Home


Related Topics:

Biological Chemistry

Current Research Articles:

Biological Chemistry


Current News

- Chemistry News

- Current Research Articles

- Job Market

- Chemistry Conferences


Chemistry A to Z

- Chemistry Index

- Chemicals

- Products and Companies


About Internetchemistry

- Internetchemistry

- Imprint


News in German News in German



Published: 13.05.2008 Get Internetchemistry RSS News Feed

Researchers uncover mechanism of action of antibiotic able to reduce neuronal cell death in brain


 
Mechanism of action of compound found to induce neurotransmitter activity in brain cells.

RICHMOND, Va. (May 9, 2008) – Virginia Commonwealth University researchers have discovered how an antibiotic works to modulate the activity of a neurotransmitter that regulates brain functions, which eventually could lead to therapies to treat Alzheimer’s disease, Huntington’s disease, epilepsy, stroke, dementia and malignant gliomas.

Neurodegenerative diseases are caused by the deterioration of neurons in the brain and spine resulting in problems related to either movement or memory. For most patients, it may be months or years before symptoms are evident because a large number of neurons die or stop functioning over a period of time. Currently, there are few treatment options for stopping this degeneration, and those currently being evaluated have shown minimal or no beneficial activity.

Ceftriaxone

Structure of Ceftriaxone

Image by Internetchemie.info

Paul B. Fisher, M.Ph., Ph.D., a professor and interim chair of the Department of Human and Molecular Genetics, and director of the VCU Institute of Molecular Medicine, in the VCU School of Medicine, and colleagues recently reported on the mechanism of action of ceftriaxone, a third-generation antibiotic with neuroprotective properties, in glutamate transport. The findings, published in the May 9 issue of the Journal of Biological Chemistry, suggest that this antibiotic or a similar drug may serve as a potential therapy against neurodegenerative disease caused by glutamate toxicity.

Glutamate is an amino acid that is important in nerve transmission and the synapse - the region that connects one neuron to another in the brain. When an excess of glutamate collects in the synapse, the result is glutamate toxicity or excitotoxicity. Ultimately, if glutamate is not cleared out of the synapse, neurons become damaged and die by a process called excitotoxicity. In previous studies, Fisher’s team identified ceftriaxone as a potent physiological stimulator of glutamate transport both in cell culture and in animal models.

“Glutamate excitotoxicity is a very important and fundamental process in neurodegeneration,” said Fisher. “Finding molecules, such as ceftriaxone, that may correct this problem can lead to preservation and increased survival of neurons in the brain and it may have direct implications in the therapy of many neurodegenerative diseases, such as in Alzheimer’s disease, stroke, ALS and epilepsy.”

In this study, Fisher and his colleagues were interested in identifying how the promoter region of the EAAT2 gene controlled the expression of glutamate in a group of brain cells called astrocytes. Using molecular biological approaches, the team examined all the regions and sequences in the promoter region and systematically eliminated them to then define which region was necessary to respond to ceftriaxone.

According to Fisher, this led the team to a critical transcription factor called nuclear factor kappaB, NF- kappaB, which regulates many functions in the brain and other parts of the body. This is a central molecule involved in regulation of genes controlling cell growth and survival. Once they identified critical regions in the EAAT2 promoter that might regulate activity, they found that alteration of one specific NF-kappaB site by mutation in the promoter was responsible for up-regulation of EAAT2 expression and consequently glutamate transport by ceftriaxone.

“This work not only has implications for the field of neurodegeneration and neurobiology, but may also help us more clearly understand brain cancer, including malignant glioma, an invariably fatal tumor, and how it impacts brain function,” said Fisher, who is the first incumbent of the Thelma Newmeyer Corman Endowed Chair in Cancer Research and researcher with the VCU Massey Cancer Center.

Future studies will examine ways to modify the structure of ceftriaxone through medicinal chemistry to create molecules that are pharmacologically improved. Currently, ceftriaxone needs to be injected, which is not the ideal for patient therapy, however, the development of an oral form would be a more preferential way to treat patients.



 

Further Information and Source:

-

Seok-Geun Lee, Zhao-Zhong Su, Luni Emdad, Pankaj Gupta, Devanand Sarkar, Alejandra Borjabad, David J. Volsky, and Paul B. Fisher:
Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes.
In: Journal of Biological Chemistry; J. Biol. Chem. 2008 283: 13116-13123. First published on March 7, 2008; DOI: 10.1074/jbc.M707697200

-

Cefatriaxone - eMolecules ID 11465983

-

Source: Virginia Commonwealth University is the largest university in Virginia and ranks among the top 100 universities in the country in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls nearly 32,000 students in 205 certificate and degree programs in the arts, sciences and humanities. Sixty-five of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 15 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers.

 

Related Information:

 

Publish your Press Release


Related topics - search form:


Google


 

Internetchemistry © 2007 - 2008 A. J. - last update 13.05.2008