Fly Model of Alexander disease points to relevance of mechanotransduction signaling (research report now available from PubMed Central)

Wang L, Xia J, Li J, Hagemann TL, Jones JR, Fraenkel E, Weitz DA, Zhang SC, Messing A, Feany MB. Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nat Commun. 2018 May 15;9(1):1899. doi:10.1038/s41467-018-04269-7. PubMed PMID: 29765022; PubMed Central PMCID: PMC5954157.

From the abstract: "... Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. ... Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis."