Neuronal insulation failure in ALS

Even before symptom onset, cells that create the insulation around neurons in the brains of human patients and mouse model of amyotrophic lateral sclerosis (ALS) die and their replacements are unable to successfully re-wrap neurons, reports a study published online this week in Nature Neuroscience. This study suggests a potential therapeutic avenue for ALS whereby promotion of the supporting cells of the nervous system can protect motor neurons from degenerating.

ALS is an adult neurodegenerative disease characterized by muscle weakness, paralysis and ultimately death. The end stage of the disease is manifested by the death of motor neurons in the cortex and spinal cord that control muscle movement. These neurons are wrapped in a special insulating layer made of specialized cells called oligodendrocytes, which are naturally replenished by oligodendrocyte progenitors (OPCs) in adulthood.

Dwight Bergles, Jeffrey Rothstein and colleagues examined post-mortem spinal cord and motor cortex from ALS patients and visualized OPCs in the brains of live mice harboring an ALS-linked mutation. They report that progressive degeneration of oligodendrocytes in the spinal cord and brain gray matter occurs before motor neuron death and disease onset. This reduction in insulation-forming cells was accompanied by an increase in OPCs that failed to mature properly. The authors also show that genetically deleting the ALS causing gene specifically in the OPCs in the mouse model of ALS can delay the onset of behavioral deterioration and prolonged their survival.