Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice

A. M. Clement; M. D. Nguyen; E. A. Roberts; M. L. Garcia; S. Boillée; M. Rule; A. P. McMahon; W. Doucette; D. Siwek; R. J. Ferrante; R. H. Brown; J.-P. Julien; L. S. B. Goldstein; D. W. Cleveland

doi:10.1126/science.1086071

Report

Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice

A. M. Clement1,3,4,*,
M. D. Nguyen5,†,
E. A. Roberts2,3,
M. L. Garcia1,3,4,
S. Boillée1,3,4,
M. Rule6,
A. P. McMahon6,
W. Doucette7,
D. Siwek8,
R. J. Ferrante8,
R. H. Brown Jr.7,
J.-P. Julien5,‡,
L. S. B. Goldstein2,3,
D. W. Cleveland1,3,4,§

¹ Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.
² Howard Hughes Medical Institute, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.
³ Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.
⁴ Department of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.
⁵ Centre for Research in Neurosciences, Research Institute of the McGill University Health Care Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.
⁶ Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
⁷ Day Neuromuscular Research Laboratory, Massachusetts General Hospital–East, Charlestown, MA 02139, USA.
⁸ Departments of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Bedford VA Medical Center, Geriatric Research Education Clinical Center, Bedford, MA 01730, USA.

↵§ To whom correspondence should be addressed. E-mail: dcleveland{at}ucsd.edu

↵* Present address: Institute for Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg-University, Duesbergweg 6, 55099 Mainz, Germany.
↵† Present address: Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
↵‡ Present address: Centre de Recherche de l'Université Laval (CHUL), Quebec, QC, Canada G1V 4G2.

See allHide authors and affiliations

Science 03 Oct 2003:
Vol. 302, Issue 5642, pp. 113-117
DOI: 10.1126/science.1086071

A. M. Clement

1 Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

4 Department of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

M. D. Nguyen

5 Centre for Research in Neurosciences, Research Institute of the McGill University Health Care Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

E. A. Roberts

2 Howard Hughes Medical Institute, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

M. L. Garcia

1 Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

4 Department of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

S. Boillée

1 Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

4 Department of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

M. Rule

6 Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

A. P. McMahon

6 Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

W. Doucette

7 Day Neuromuscular Research Laboratory, Massachusetts General Hospital–East, Charlestown, MA 02139, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

D. Siwek

8 Departments of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Bedford VA Medical Center, Geriatric Research Education Clinical Center, Bedford, MA 01730, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

R. J. Ferrante

8 Departments of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Bedford VA Medical Center, Geriatric Research Education Clinical Center, Bedford, MA 01730, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

R. H. Brown Jr.

7 Day Neuromuscular Research Laboratory, Massachusetts General Hospital–East, Charlestown, MA 02139, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

J.-P. Julien

5 Centre for Research in Neurosciences, Research Institute of the McGill University Health Care Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

L. S. B. Goldstein

2 Howard Hughes Medical Institute, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

D. W. Cleveland

1 Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

3 Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

4 Department of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA 92093–0670, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Article
Figures & Data
Info & Metrics
eLetters
PDF

You are currently viewing the abstract.

View Full Text

Log in to view the full text

via AAAS login

AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Become an AAAS Member
Activate your Account
Purchase Access to Other Journals in the Science Family
Account Help

As a service to the community, this article is available for free. Existing users log in.

Become a AAAS member
Account help

Log in through your institution

More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

This article has a correction. Please see:

Is corrected by - October 24, 2003

Abstract

The most common form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant–expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.

View Full Text

Amyotrophic lateral sclerosis does not develop if nerve cells with the mutation for the disease are surrounded by nonneural cells that lack the mutation.

Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice

This article has a correction. Please see:

Abstract

Science

Article Tools