Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice.
The most common inherited [correct] 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.
Clement
A M
AM
Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093-0670, USA.
Nguyen
M D
MD
Roberts
E A
EA
Garcia
M L
ML
Boillée
S
S
Rule
M
M
McMahon
A P
AP
Doucette
W
W
Siwek
D
D
Ferrante
R J
RJ
Brown
R H
RH
Julien
J-P
JP
Goldstein
L S B
LS
Cleveland
D W
DW
D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000473:pathology; D002470:Cell Survival; D002678:Chimera; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D009154:Mutation; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D025801:Ubiquitin / Q000032:analysis
D016900:Neurofilament Proteins; C000606290:SOD1 protein, human; D025801:Ubiquitin; C044882:neurofilament protein L; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1