Featured Research

from universities, journals, and other organizations

Mechanism Of Action Of Antibiotic Able To Reduce Neuronal Cell Death In Brain Uncovered

Date:
May 12, 2008
Source:
Virginia Commonwealth University
Summary:
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.

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.

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.

This work was supported by a program project grant from the National Institutes of Health, Neurology and Stroke, and the Samuel Waxman Cancer Research Foundation.

Fisher worked with a team that included: Seok-Geun Lee, Ph.D., lead author of the paper and assistant professor, and Zaozhong Su, Ph.D., associate professor, both in the VCU Department of Human and Molecular Genetics; Devanand Sarkar, MBBS, Ph.D., assistant professor and Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center and Department of Human and Molecular Genetics; and David J. Volsky, Ph.D., professor, St. Luke's Roosevelt Hospital Center, Columbia University in New York.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Commonwealth University. "Mechanism Of Action Of Antibiotic Able To Reduce Neuronal Cell Death In Brain Uncovered." ScienceDaily. ScienceDaily, 12 May 2008. <www.sciencedaily.com/releases/2008/05/080509145457.htm>.
Virginia Commonwealth University. (2008, May 12). Mechanism Of Action Of Antibiotic Able To Reduce Neuronal Cell Death In Brain Uncovered. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2008/05/080509145457.htm
Virginia Commonwealth University. "Mechanism Of Action Of Antibiotic Able To Reduce Neuronal Cell Death In Brain Uncovered." ScienceDaily. www.sciencedaily.com/releases/2008/05/080509145457.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins