When delivered to animals, the beta-lactam ceftriaxone increased both brain expression of GLT1 and its biochemical and functional activity. beta-Lactams and various semi-synthetic derivatives are potent antibiotics that act to inhibit bacterial synthetic pathways. Furthermore, this action appears to be mediated through increased transcription of the GLT1 gene.
Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, we discovered that many beta-lactam antibiotics are potent stimulators of GLT1 expression. Animal studies show that the protein is important for normal excitatory synaptic transmission, while its dysfunction is implicated in acute and chronic neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, brain tumours and epilepsy. In spite of its critical importance in normal and abnormal synaptic activity, no practical pharmaceutical can positively modulate this protein. Inactivation of synaptic glutamate is handled by the glutamate transporter GLT1 (also known as EAAT2 refs 1, 2), the physiologically dominant astroglial protein. Glutamate is the principal excitatory neurotransmitter in the nervous system. Thus these studies provide a class of potential neurotherapeutics that act to modulate the expression of glutamate neurotransmitter transporters via gene activation. When used in an animal model of the fatal disease ALS, the drug delayed loss of neurons and muscle strength, and increased mouse survival. Ceftriaxone was neuroprotective in vitro when used in models of ischaemic injury and motor neuron degeneration, both based in part on glutamate toxicity.
Glutamate transporters are important in preventing glutamate neurotoxicity. When delivered to animals, the β-lactam ceftriaxone increased both brain expression of GLT1 and its biochemical and functional activity. β-Lactams and various semi-synthetic derivatives are potent antibiotics that act to inhibit bacterial synthetic pathways. Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, we discovered that many β-lactam antibiotics are potent stimulators of GLT1 expression. from the University of California, Berkeley.Glutamate is the principal excitatory neurotransmitter in the nervous system. from the University of Chicago Law School, and his M.B.A. Reese also worked with a variety of organizations ranging from new ventures to internationally-renowned business think tanks to Fortune 500 companies. (2004), ATA Airlines Corp., PG&E National Energy Group, Inc., Solutia, Inc., USGen New England, Inc., Midway Airlines Corp., and Venture Holdings LLC. Reese also represented creditors, investors, acquirers and other interested parties in numerous other cases, including the chapter 11 cases of US Airways, Inc. (2002), Delphi Corporation, Washington Group International, Inc., and Enron Corporation as debtors and debtors-in-possession. During that time, he represented clients in many large and complex chapter 11 cases, including representing US Airways Group, Inc. Randall Reese founded Restructuring Concepts LLC after spending nearly six years with the international law firm of Skadden, Arps, Slate, Meagher & Flom LLP in its Corporate Restructuring practice group.
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