Figure 6.

Consequences of PLP1 duplication on the cellular physiology. When overexpressed, PLP1 sequesters cholesterol and accumulates in late endosomes and lysosomes. Moreover, raft formation and membrane trafficking are crucial for myelin formation, and their disruption causes the loss of myelin. In addition to its cytotoxic effects, PLP1 protein overexpression leads to an inflammatory response with the activation of microglia in white and grey matter and the upregulation of cytokines and their receptors. It is probable that the microglial activation and the inflammatory response contribute to a certain extent to the pathology’s development and progression.