ALS: astrocytes move in as deadly neighbors

@article{Julien2007ALSAM,
  title={ALS: astrocytes move in as deadly neighbors},
  author={Jean-Pierre Julien},
  journal={Nature Neuroscience},
  year={2007},
  volume={10},
  pages={535-537}
}
  • J. Julien
  • Published 1 May 2007
  • Biology
  • Nature Neuroscience
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons. Two independent studies in this issue show that astrocytes expressing a mutation in the enzyme superoxide dismutase can exacerbate motor neuron death, supporting previous suggestions that non-neuronal cells contribute to ALS pathogenesis. 
Understanding ALS: new therapeutic approaches
TLDR
The pathogenic mechanisms associated with ALS are reviewed, and the strengths and limitations of some new therapeutic approaches are discussed.
Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis
Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any
Molecular and Cellular Insights: Neuroinflammation and Amyotrophic Lateral Sclerosis
TLDR
This chapter will focus on the precise understanding of neuroinflammatory responses in molecular pathomechanism of ALS and it also discusses new potential therapeutic strategies to improve neuroprotection and to alleviate proteotoxicity in ALS linked motor neurodegeneration.
State of the art and the dark side of amyotrophic lateral sclerosis.
  • A. Musarò
  • Biology
    World journal of biological chemistry
  • 2010
TLDR
Views about ALS pathogenesis are now enriched by the recent discovery of mutations in a pair of DNA/RNA-binding proteins called TDP-43 and FUS/TLS as causes of familial and sporadic forms of ALS.
Current hypotheses for the underlying biology of amyotrophic lateral sclerosis
TLDR
It is demonstrated that mutations and pathology associated with the TDP‐43 gene and protein may be more common than SOD1 mutations in familial and sporadic ALS, and Convergence of these pathways is likely to mediate disease onset and progression.
Amyotrophic lateral sclerosis: new insights into underlying molecular mechanisms and opportunities for therapeutic intervention.
TLDR
New envisaged models and tools may offer unforeseen clues on the etiology of this disease and hopefully provide the key to treatment.
Glial cells in ALS: the missing link?
Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review
TLDR
A review examines the possible roles of nicotinamide riboside and pterostilbene as therapeutic strategies in ALS and proposes treatment with antioxidants to combat the characteristic OS and the regeneration of Nicotinamide adenine dinucleotide levels by the use of precursors.
Enzymatic and proteomic analysis of spinal cord in a G93A ALS mouse model
TLDR
It is demonstrated that Motexafin Gadolinium (MGd), an organometallic compound, markedly extends survival in G93A mice, a well-established, standardized mouse model of ALS used to elucidate molecular mechanisms of disease and the efficacy of proposed new therapeutic treatments for ALS.
...
...

References

SHOWING 1-10 OF 16 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.
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.
Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis
TLDR
It is demonstrated that the expression of mSOD1G93A results in activated and neurotoxic microglia, and suggested that the lack of m SOD1 G93A expression inmicroglia may contribute to motoneuron protection, and confirmed the importance of microglio as a double-edged sword.
Restricted Expression of G86R Cu/Zn Superoxide Dismutase in Astrocytes Results in Astrocytosis But Does Not Cause Motoneuron Degeneration
TLDR
Results indicate that 21q linked FALS is not a primary disorder of astrocytes, and that expression of mutant SOD1 restricted to astroCytes is not sufficient to cause motoneuron degeneration in vivo.
Absence of Tumor Necrosis Factor-α Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutations
TLDR
Surprisingly, the absence of TNF-α did not affect the lifespan or the extent of motor neuron loss in SOD1 transgenic mice, indicating that T NF-α does not directly contribute to motor neuron degeneration caused by S OD1 mutations.
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TLDR
Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Efficient three‐drug cocktail for disease induced by mutant superoxide dismutase
TLDR
Results indicate that a combination approach consisting of three drugs for distinct targets in the complex pathway to neuronal death, minocycline, riluzole, and nimodipine may represent an effective strategy for ALS treatment.
Non–cell autonomous effect of glia on motor neurons in an embryonic stem cell–based ALS model
TLDR
The studies demonstrate that glial cells carrying a human SOD1G93A mutation have a direct, non–cell autonomous effect on motor neuron survival and show that ESC-based models of disease provide a powerful tool for studying the mechanisms of neural degeneration.
Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis
Here we report that chromogranins, components of neurosecretory vesicles, interact with mutant forms of superoxide dismutase (SOD1) that are linked to amyotrophic lateral sclerosis (ALS), but not
Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis
TLDR
It is proposed that immunization strategies should be considered as potential avenues for treatment of familial ALS caused by SOD1 mutations after emerging evidence for the existence of secretory pathways for superoxide dismutase (SOD1) mutants linked to amyotrophic lateral sclerosis (ALS).
...
...