Navigation Links
Researchers uncover mechanism of action of antibiotic able to reduce neuronal cell death in brain
Date:5/9/2008

Research Highlights:

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

  • The findings may lead researchers to develop potential novel therapies to treat Alzheimer's disease, amyotrophic lateral sclerosis, Huntingtons disease, epilepsy, stroke/ischemia, dementia and malignant gliomas

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 Alzheimers disease, Huntingtons 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.

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, Fishers 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 Alzheimers 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.


'/>"/>

Contact: Sathy Achia Abraham
sbachia@vcu.edu
804-827-0890
Virginia Commonwealth University
Source:Eurekalert

Related biology news :

1. Researchers identify proteins involved in new neurodegenerative syndrome
2. Texas researchers and educators head for Antarctica
3. MGH researchers describe new way to identify, evolve novel enzymes
4. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
5. U of MN researchers discover noninvasive diagnostic tool for brain diseases
6. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
7. Researchers discover new strategies for antibiotic resistance
8. Researchers find new taste in fruit flies: carbonated water
9. Binghamton University researchers investigate evolving malaria resistance
10. UIC researchers find promising new targets for antibiotics
11. Researchers develop simple method to create natural drug products
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/20/2016)... DALLAS , June 20, 2016 ... criminal justice technology solutions for public safety, investigation, ... by the prisons involved, it has secured the ... Corrections (DOC) facilities for Managed Access Systems (MAS) ... (4) additional facilities to be installed by October, ...
(Date:6/9/2016)... 2016 Paris Police Prefecture ... security solution to ensure the safety of people and operations ... the major tournament Teleste, an international technology group ... announced today that its video security solution will be utilised ... up public safety across the country. The system roll-out is ...
(Date:6/2/2016)... YORK , June 2, 2016   The Weather ... is announcing Watson Ads, an industry-first capability in which consumers ... by being able to ask questions via voice or text ... Marketers have long sought ... the consumer, that can be personal, relevant and valuable; and ...
Breaking Biology News(10 mins):
(Date:12/5/2016)... LAKE, N.J. , Dec. 5, 2016 /PRNewswire/ ... Phase 3 open-label two-year study of rufinamide, which ... the American Epilepsy Society (AES) held from December ... Analysis of final two-year safety, tolerability and cognitive ... with rufinamide experienced similar safety and tolerability profiles, ...
(Date:12/4/2016)...  In five studies being presented today during the ... Exposition in San Diego , researchers ... delivery of life-saving treatments to patients with a variety ... carry therapies directly to the sites in the body ... substantial advantage over traditional, systemic methods. The studies highlight ...
(Date:12/2/2016)... OAKS, Calif. , Dec. 2, 2016 Amgen ... AGN ) today announced the submission of a Marketing ... ABP 215, a biosimilar candidate to Avastin ® (bevacizumab). ... application submitted to the EMA. "The submission ... as Amgen seeks to expand our oncology portfolio," said ...
(Date:12/2/2016)... ... December 01, 2016 , ... Aerocom Healthcare ( ... hospitals, will present its chain-of-custody solution for tracking and securing medications at booth ... Dec. 4-8, 2016. , Aerocom has a proven solution for tracking medications via ...
Breaking Biology Technology: