Alexander Disease: A Guide for Patients and Families

GFAP at 50

“…conditions, they are particularly abundant in Alexander disease. These aggregates are complex mixtures of GFAP, other intermediate filaments including vimentin and synemin, stress proteins including aB-crystallin and heat shock protein 27, and other recently described components such as cyclin D2 (Perng et al, 2006;Heaven et al, 2016;Messing, 2018b). The early stages of Rosenthal fiber formation are not yet clear, but they may arise from stress granules (Heaven et al, 2016) or involve focal deposits on existing intermediate filaments along with aB-crystallin (Sosunov et al, 2017).…”

“…Among the most convincing examples of GFAP expression in nonastrocytic cells are nonmyelinating Schwann cells, enteric glia, and the neurogenic stem cells of the subgranular zone in the hippocampus and the subventricular zone surrounding the lateral ventricles. Other sites of GFAP expression, some still speculative, include stellate cells of the liver, pancreas, and vocal fold, Leydig and Sertoli cells in the testis, lens epithelium, lymphocytes, and vertebral and tracheal cartilage (for review, see Messing, 2018b). In the setting of cancer, several surprising examples occur, such as salivary gland tumors and myoepithelial tumors of soft tissue (Huang et al., 1996; Jo and Fletcher, 2015).…”

“…Prevalence was calculated at 1 in 2.7 million for the population of Japan, although this is certain to be an underestimate (Yoshida et al., 2011). Extensive reviews have appeared that are comprehensive (Brenner et al., 2009; Flint and Brenner, 2011; Messing, 2018b) or limited to particular aspects of the disease, such as clinical features (Pareyson et al., 2008; Balbi et al., 2010), neuroinflammation (Olabarria and Goldman, 2017), or genetics (Messing, 2018a). Here, we focus on the most recent findings, which mainly represent attempts to determine mechanisms of the disease.…”