Researchers have discovered a cellular “switch” that regulates the production of the correct amount of fat molecules needed for cells to create the myelin layer that protects neurons.
The switch was found to rely on the fatty acid synthase enzyme, or FASN, which, when absent or inactive, leads to defective nerve cells’ myelin protection and impaired motor function. This finding may open doors for new research to prevent demyelination, a phenomenon involved in the development of diseases such as Charcot-Marie-Tooth disease.
“Knowing how reduced lipid [fat molecule] synthesis affects myelination during development is an important step towards gaining a better understanding of how these [demyelinating] diseases progress,” Laura Montani, PhD, lead author of the study, said in an ETH Zurich news release written by Peter Rüegg.
A team led by researchers at ETH Zürich genetically engineered mice to lack the FASN enzyme specifically in Schwann cells. The mice showed decreased muscle strength and reduced balance, which strongly suggested that FASN played a role in the regulation of Schwann cells and peripheral nerve cell activity.
Further evaluation of mice development showed the absence of the enzyme did not change the proliferation rate or survival of Schwann cells. However, older mice showed significant demyelination, suggesting impaired myelin production.
The team found that Schwann cells self-produce about half of the fat molecules needed for building up the myelin sheath, with the additional fat molecules needed acquired from food consumption.
In the absence of FASN, fat synthesis was severely impaired as well as the process of myelin production, an outcome that a high-fat diet was unable to overcome. In addition, FASN was seen to regulate several signals important to the myelin building process.
The results of the study showed that FASN activity and intrinsic fat molecules production by Schwann cells are essential for the formation of myelin sheaths in peripheral nerve cells.
“Overall these findings provide fundamentally novel information about the regulation of myelination, establishing the basis for future studies,” the researchers wrote.
Additional studies addressing FASN-mediated processes under different conditions in peripheral nerves, such as in diseases and after injury, are still needed, they added.
These findings were reported in the study, “De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination,” published in the Journal of Cell Biology.