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Toxic Factor Linked to ALS Neuron Death

Michael Smith
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine. | April 25, 2007

Instead, he said, "they are major players. The astrocytes and their cellular environment are specifically causing motor neuron death" while sparing other forms of neuron.

Some cases of familial ALS are associated with mutations in the gene coding for the enzyme superoxide dismutase. In cell culture experiments, using mouse cells, both research groups showed that:

  • When grown together with mutated glial cells, motor neurons died whether or not they themselves expressed the superoxide dismutase mutation.
  • Other types of neurons -- such as primary spinal GABAergic neurons -- were not affected when grown with mutated glial cells.

Dr. Przedborski and colleagues also reported that astrocytes are the only glial cells with the toxic effect. Fibroblasts, microglia, cortical neurons and myocytes expressing mutated superoxide dismutase "do not cause overt neurotoxicity," they reported.

Motor neurons expressing mutated forms of superoxide dismutase have structural changes, both groups reported -- they are smaller and have fewer long axons than wild-type neurons.

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