![]() 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. 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 β-lactam antibiotics are potent stimulators of GLT1 expression. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.Glutamate is the principal excitatory neurotransmitter in the nervous system. The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved.
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