Could mutations in PLP initiate MS?

Myelin proteolipid protein (PLP) is the most abundant protein component of central nervous system myelin and is essential for maintenance and structure of the myelin. The gene that makes PLP, ‘PLP1’, is located on the X chromosome, with mutations manifesting in males as Pelizaeus-Merzbacher disease (PMD), where myelin production is highly disrupted. Females are generally non-symptomatic carriers, as they carry two copies of the X chromosome and usually only one carries the mutation.

However, two recent reports described individuals diagnosed with MS who also carry PLP1 gene mutations. These mutations differ from those found to cause PMD. How these mutations may relate to the development of MS in these individuals is unclear. We know from research in PMD that some mutations in the PLP1 gene can cause PLP protein to accumulate within the body of myelin producing cells (oligodendrocytes), causing damage and even death of these cells. This study investigates whether or not the PLP1 gene mutations that have been found in MS patients could directly damage oligodendrocytes, and therefore contribute to disease development.