Frontier: ALS Due to Fallen “Stars”?

by Elizabeth Norton Lasley

May, 2007

ALS due to fallen “stars”? The star-shaped cells known as astrocytes play many supportive roles in the brain. But a growing body of research suggests that astrocytes also contribute to neurodegenerative disease—in particular, amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

ALS destroys motor neurons, leading to paralysis. Because 90 percent of cases are sporadic (with no family history), few genes have emerged to give clues to the disease’s development.

In some patients, the motor neurons themselves have a mutation in the gene encoding the enzyme superoxide dismutase-1 (SOD). Some studies have found that healthy motor neurons begin to show characteristics of ALS when cultured with nonneuronal cells carrying the mutation. Just which cells remained unclear.

Two studies in the May Nature Neuroscience point to astrocytes. Working with a mouse model of ALS, Serge Przedborski and colleagues at Columbia University found that motor neurons carrying the human SOD mutation showed some abnormalities, but not neurodegeneration. However, astrocytes with the mutation triggered cell death in cultured motor neurons, following the same steps as the pathway of degeneration found in ALS.

Kevin Eggan and colleagues at Harvard University and Perugia University in Italy generated motor neurons from embryonic stem cells of “transgenic” mice with either the normal, human SOD gene or the mutated version. Both the normal and mutated motor neurons showed signs of neurodegeneration when cultured with astrocytes carrying the mutation.

By showing that ALS may result from factors not intrinsic to the motor neuron, such as astrocytes, the findings may open new routes to treatment, Eggan says. “Our work may also lead to new lines of stem cells that could allow us to study sporadic ALS,” he adds.