Cholesterol Biosynthesis Supports Myelin Gene Expression and Axon Ensheathment through Modulation of P13K/Akt/mTor Signaling.

The speed of electrical impulse movement through axons is increased by myelin, a specialized, cholesterol-rich glial cell membrane that tightly wraps axons. During development, myelin membrane grows dramatically, suggesting a significant demand on mechanisms that produce and assemble myelin components, while it spirally wraps axons. Our studies indicate that cholesterol is necessary for both myelin growth and axon wrapping. Specifically, we found that cholesterol facilitates signaling mediated by the PI3K/Akt/mTOR pathway, a powerful driver of myelination. Because mTOR promotes the expression of genes necessary for cholesterol synthesis, cholesterol formation and PI3K/Akt/mTOR signaling might function as a feedforward mechanism to produce the large amounts of myelin membrane necessary for axon ensheathment.