Toxicity Pathways in ALS
Excitotoxicity and Amyotrophic Lateral Sclerosisvan Cutsem P. · Dewil M. · Robberecht W. · van den Bosch L.
Neurobiology, Campus Gasthuisberg, Leuven, Belgium
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Since its description by Charcot more than 130 years ago, the pathogenesis of selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains unsolved. Over the years, many pathogenic mechanisms have been proposed. Amongst others these include: oxidative stress, excitotoxicity, aggregate formation, inflammation, growth factor deficiency and neurofilament disorganization. This multitude of contributing factors indicates that ALS is a complex disease and also suggests that ALS is a multifactorial disorder. Excitotoxicity is not the newest and most spectacular hypothesis in the ALS field, but it is undoubtedly one of the most robust pathogenic mechanisms supported by an impressive amount of evidence. Moreover, the therapeutic efficacy of riluzole, the only drug proven to slow disease progression in ALS, is most likely related to its anti-excitotoxic properties. In this review, we will give an overview of the arguments in favor of the involvement of excitotoxicity in ALS and of the possible mechanisms leading to motor neuron death. We will also summarize the intrinsic properties of motor neurons that render these cells particularly vulnerable to excitotoxicity and could explain the selective vulnerability of motor neurons in ALS. All this information could help to develop new and better therapeutic strategies that could protect motor neurons from excitotoxicity.
© 2005 S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. 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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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. 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. 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). 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. 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.