Oligodendroglia and myelin pathology in fragile X syndrome.

ABSTRACT

Studies of the pathophysiology of fragile X syndrome (FXS) have predominantly focused on synaptic and neuronal disruptions in the disease. However, emerging studies highlight the consistency of white matter abnormalities in the disorder. Recent investigations using animal models of FXS have suggested a role for the fragile X translational regulator 1 protein (FMRP) in the development and function of oligodendrocytes, the myelinating cells of the central nervous system. These studies are starting to uncover FMRP's involvement in the regulation of myelin-related genes, such as myelin basic protein, and its influence on the maturation and functionality of oligodendrocyte precursor cells and oligodendrocytes. Here, we consider evidence of white matter abnormalities in FXS, review our current understanding of FMRP's role in oligodendrocyte development and function, and highlight gaps in our knowledge of the pathogenic mechanisms that may contribute to white matter abnormalities in FXS. Addressing these gaps may help identify new therapeutic strategies aimed at enhancing outcomes for individuals affected by FXS.