Neurodegenerative Dis 2004;1:245–254
(DOI:10.1159/000085063)

Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target

Dupuis L.a, b · Gonzalez de Aguilar J.-L.a · Oudart H.c · de Tapia M.a · Barbeito L.b · Loeffler J.-P.a
aLaboratoire de Signalisations Moléculaires et Neurodégénérescence, U692 INSERM, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France; bInstituto de Investigaciones Biologicas Clemente Estable, Montevideo, Uruguay; cCEPE, CNRS UPR9010, Strasbourg, France
email Corresponding Author


 goto top of outline Key Words

  • Amyotrophic lateral sclerosis
  • Mitochondria
  • Uncoupling protein
  • Energy homeostasis
  • SOD1
  • Skeletal muscle
  • Motor neuron

 goto top of outline Abstract

Strong evidence shows that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis (ALS), but despite the fact that mitochondria play a central role in excitotoxicity, oxidative stress and apoptosis, the intimate underlying mechanism linking mitochondrial defects to motor neuron degeneration in ALS still remains elusive. Morphological and functional abnormalities occur in mitochondria in ALS patients and related animal models, although their exact nature and extent are controversial. Recent studies postulate that the mislocalization in mitochondria of mutant forms of copper-zinc superoxide dismutase (SOD1), the only well-documented cause of familial ALS, may account for the toxic gain of function of the enzyme, and hence induce motor neuron death. On the other hand, mitochondrial dysfunction in ALS does not seem to be restricted only to motor neurons as it is also present in other tissues, particularly the skeletal muscle. The presence of this ‘systemic’ defect in energy metabolism associated with the disease is supported in skeletal muscle tissue by impaired mitochondrial respiration and overexpression of uncoupling protein 3. In addition, the lifespan of transgenic mutant SOD1 mice is increased by a highly energetic diet compensating both the metabolic defect and the motorneuronal function. In this review, we will focus on the mitochondrial dysfunction linked to ALS and the cause-and-effect relationships between mitochondria and the pathological mechanisms thought to be involved in the disease.

Copyright © 2004 S. Karger AG, Basel


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 goto top of outline Author Contacts

Jean-Philippe Loeffler
Laboratoire de Signalisations Moléculaires et Neurodégénérescence
U692 INSERM, Université Louis Pasteur, Faculté de Médecine, 11 rue Humann
FR–67085 Strasbourg (France)
Tel. +33 390 243081, Fax +33 390 243065, E-Mail loeffler@neurochem.u-strasbg.fr


 goto top of outline Article Information

Received: September 27, 2004
Accepted after revision: January 24, 2005
Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 0, Number of References : 108


 goto top of outline Publication Details

Neurodegenerative Diseases

Vol. 1, No. 6, Year 2004 (Cover Date: Released May 2005)

Journal Editor: Nitsch, R.M. (Zürich)
ISSN: 1660–2854 (print), 1660–2862 (Online)

For additional information: http://www.karger.com/ndd


Copyright / Drug Dosage / Disclaimer

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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 goverment 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.