The multifaceted role of glial cells in amyotrophic lateral sclerosis

@article{Valori2013TheMR,
  title={The multifaceted role of glial cells in amyotrophic lateral sclerosis},
  author={Chiara F Valori and Liliana Brambilla and Francesca Martorana and Daniela Rossi},
  journal={Cellular and Molecular Life Sciences},
  year={2013},
  volume={71},
  pages={287-297}
}
Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as… Expand
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References

SHOWING 1-10 OF 128 REFERENCES
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
TLDR
Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS. Expand
Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy
TLDR
Searches for future therapeutic options should aim at compensating disturbed functions of oligodendrocytes, astrocyte and microglial cells, by which at least some aspects of the pathophysiology of the very inhomogeneous clinical syndrome of schizophrenia might be explained. Expand
Live imaging of amyotrophic lateral sclerosis pathogenesis: Disease onset is characterized by marked induction of GFAP in Schwann cells
TLDR
The results suggest that the disease in mice is initiated simultaneously in the spinal cord and in the peripheral nerves and is characterized by several cycles of GFAP upregulation, and peripheral nerves pathology/denervation and associated Schwann cell stress may play an important role in the ALS pathogenesis. Expand
Focal degeneration of astrocytes in amyotrophic lateral sclerosis
TLDR
It is proposed that excitotoxicity in ALS affects both motor neurons and astrocytes, favouring their local interactive degeneration, and this new mechanistic hypothesis has implications for therapeutic interventions. Expand
Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis.
TLDR
The involvement of oligodendrocytes and their progenitor cells in the ventral grey matter of the spinal cord in amyotrophic lateral sclerosis and Mutant superoxide dismutase 1 was found to directly affect monocarboxylate transporter 1 protein expression are reported. Expand
Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
TLDR
Isolation of astrocytes with aberrant phenotype from primary spinal cord cultures of symptomatic rats expressing the SOD1G93A mutation is reported, finding that AbA cells appear to be an as-yet unknownAstrocyte population arising during ALS progression with unprecedented proliferative and neurotoxic capacity and may be potential cellular targets for slowing ALS progression. Expand
Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons
TLDR
It is demonstrated that astrocytes derived from postmortem tissue from both FALS and SALS patients are similarly toxic to motor neurons and that SOD1 is a viable target for SALS, as its knockdown significantly attenuatesAstrocyte-mediated toxicity toward motor neurons. Expand
Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice
TLDR
Results reinforce the important balance between specific protective/injurious inflammatory immune responses in modulating clinical outcomes and suggest that the delayed forelimb motor weakness in ALS mice is partially explained by augmented protective responses in the cervical spinal cords. Expand
Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis.
TLDR
Altered properties of astrocytes are likely to play a crucial role in the propagation of motoneuron injury in superoxide dismutase 1-related amyotrophic lateral sclerosis and indicate that manipulation of the energy supply to motoneurons as well as inhibition of p75 receptor signalling may represent valuable neuroprotective strategies. Expand
Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration
TLDR
It is demonstrated that while normal astrocyte function is an important factor in the etiology of motor neuron diseases such as ALS, astroCyte proliferation itself does not play a significant role. Expand
...
1
2
3
4
5
...