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."