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}
}

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References

SHOWING 1-10 OF 297 REFERENCES

Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia

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.

Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1

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.

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.

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.

Slowing of axonal transport is a very early event in the toxicity of ALS–linked SOD1 mutants to motor neurons

Reduced transport of selective cargoes of slow transport, especially tubulin, arises months before neurodegeneration in two SOD1 mutations linked to familial ALS, verifying the hypothesis that damage to the cargoe or machinery ofslow transport is an early feature of toxicity mediated by mutant SOD 1.

Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS.

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.

The neuroprotective factor Wlds does not attenuate mutant SOD1-mediated motor neuron disease

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.

Increased cytotoxic potential of microglia from ALS‐transgenic mice

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.
...