Over the past 30 years, astrocytes have emerged from a supporting role to co-starring with neurons and oligodendrocytes as players in CNS disorders. Dysfunction of astrocytes is now implicated in disorders once thought to be solely of neuronal origin, such as epilepsy, amyotrophic lateral sclerosis, and depression. It is also implicated in disorders previously ascribed solely to oligodendrocytes, like multiple sclerosis, vanishing white matter disease, and megalencephalic leukoencephalopathy with subcortical cysts. In some instances, the disease cause is a defect originating in astrocytes. The first and perhaps most definitive example is Alexander disease, in which coding mutations in the GFAP gene can cause massive dysmyelination and perturb multiple neuronal circuits. In other instances, induced disruption of normal astrocyte functions, such as glutamate or potassium transport, exacerbates...
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