ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors

@article{Boille2006ALSAD,
  title={ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors},
  author={S{\'e}verine Boill{\'e}e and Christine Vande Velde and Don W. Cleveland},
  journal={Neuron},
  year={2006},
  volume={52},
  pages={39-59}
}
Amyotrophic lateral sclerosis is a late-onset progressive neurodegenerative disease affecting motor neurons. The etiology of most ALS cases remains unknown, but 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1). Since sporadic and familial ALS affects the same neurons with similar pathology, it is hoped that therapies effective in mutant SOD1 models will translate to sporadic ALS. Mutant SOD1 induces non-cell-autonomous motor neuron killing by an unknown gain of toxicity… Expand
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References

SHOWING 1-10 OF 293 REFERENCES
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
TLDR
Onset and progression of amyotrophic lateral sclerosis represent distinct disease phases defined by mutant action within different cell types to generate non–cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells. Expand
Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1
  • Jiming Kong, Zuoshang Xu
  • Biology, Medicine
  • The Journal of Neuroscience
  • 1998
TLDR
The absence of massive motor neuron death at the early stages of the disease indicates that the majority of motor neurons could be rescued after clinical diagnosis, and indicates that mutant SOD1 toxicity is mediated by damage to mitochondria in motor neurons. Expand
ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions
TLDR
It is reported here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity. Expand
Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS
TLDR
It is hypothesized that astrocytic activation may exert a trophic influence on the motor neurons that is insufficiently maintained late in the course of the disease, and agents which inhibit microglia may help to limit disease progression. Expand
An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe,Expand
Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant.
TLDR
By deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is reduced. Expand
Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice
TLDR
Nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons. Expand
Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS.
TLDR
Evidence is provided that dysregulation of Nrf2 and the ARE, coupled with reduced pentose phosphate pathway activity and decreased generation of NADPH, represent significant and hitherto unrecognized components of the toxic gain of function of mutant SOD1. Expand
The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease
TLDR
Despite its effectiveness in delaying axonal loss in other neurodegenerative models, the presence of Wlds did not slow disease onset, ameliorate mutant motor neuron death, axonal degeneration, or preserve synaptic attachments in mice that develop disease from ALS-linked S OD1 mutants SOD1G37R or SOD 1G85R. Expand
Increased cytotoxic potential of microglia from ALS‐transgenic mice
TLDR
It is found that mtSOD1 expression increases the production of TNF‐α and attenuates IL‐6‐release by LPS‐activated adult microglia, and suggests an increased cytotoxic potential of adult mtS OD1 microGLia, which only becomes apparent after microglial activation. Expand
...
1
2
3
4
5
...