Reducing SOD1 mutant expression in these cells doubled the lifetime but did not slow disease onset or early progression, according to Nature Neuroscience paper.
Scientists report that in mice SOD1 mutation affects astrocytes, which could make a viable target for slowing Lou Gehrig’s disease progression.
The investigators previously showed that in the early stages of inherited ALS, the SOD1 protein damages microglia. These immune cells were then observed to significantly accelerate the degeneration of the motor neurons.
The new study demonstrates that a similar thing happens to astrocytes, support cells that are essential to neuronal function. The researchers speculate that the nonneuronal cells play a role in nourishing the motor neurons and in scavenging toxins from the cellular environment. As with microglia, the helper role of astrocytes is altered due to mutations in the SOD1 protein.
“We tested what would happen if we removed the mutant gene from astrocytes in mouse models,” says Don Cleveland, Ph.D., one of the authors and University of California, San Diego (UCSD) professor of medicine, neurosciences, and cellular and molecular medicine. “What happened was it doubled the lifespan of the mouse after the onset of ALS.”
Reduction of the disease-causing mutant SOD1 in astrocytes did not slow disease onset or early progression, the scientists note. The late stage of the disease, however, was extended.
“Silencing the mutant gene in the astrocytes not only helps protect the motor neuron, but delays activation of mutant microglia that act to accelerate the progression of ALS,” adds Dr. Cleveland.
Aside from UCSD, the research also included investigators from RIKEN Brain Science Institute, Washington University School of Medicine, Kyoto University, and Kyoritsu University of Pharmacy. The study appeared in the advance online publication of Nature Neuroscience on February 3.