NDRG1

The NDRG1 gene provides instructions for making a protein whose function is not well understood. The NDRG1 protein may play a role in arresting cell growth and prompting cells to mature and assume specialized functions (differentiate). It probably performs these roles by shuttling signals between the nucleus and other parts of the cell. The NDRG1 protein also interacts with other proteins that help regulate the distribution of fats (lipids) in the body.

The NDRG1 gene is active in cells throughout the body, but its activity is particularly high in specialized cells called Schwann cells. Schwann cells nourish and protect nerve cells, especially the cell extensions (axons) that transmit nerve impulses. Schwann cells also produce myelin, a fatty substance that covers axons and promotes the efficient transmission of nerve impulses. Scientists speculate that the NDRG1 protein is involved in Schwann cell differentiation, myelin maintenance, and the signaling necessary for the survival of nerve axons.

Charcot-Marie-Tooth disease - caused by mutations in the NDRG1 gene

Researchers have identified two NDRG1 mutations that cause a form of Charcot-Marie-Tooth disease known as type 4D. Both mutations alter the structure of the NDRG1 protein by producing an abnormally small protein or a protein that is missing a critical segment. The altered structure probably causes a loss of the protein's function.

It is unclear how NDRG1 mutations lead to type 4D Charcot-Marie-Tooth disease. Schwann cells use large amounts of lipids and proteins to make myelin, and they rely on a sufficient supply of these substances. NDRG1 mutations may impair the NDRG1 protein's interactions with other proteins that help distribute lipids in the body. As a result, the supply of lipids to Schwann cells may be disrupted, affecting myelin production and altering the transmission of nerve impulses. NDRG1 mutations may also disturb signaling that is necessary for the survival of axons. Loss of myelin and problems with nerve transmission are signs of type 4D Charcot-Marie-Tooth disease.