Astrocyte dysfunction contributes to neuronal death in ALS and other neurodegenerative diseases, but the precise mechanisms of toxicity are not well understood (see Oct 2011 news). Mel Feany and colleagues at the Brigham and Women’s Hospital in Boston, MA, have taken a step toward identifying pathways mediating glia-induced neuronal death by developing a fruit fly model of Alexander disease, a neurodegenerative disease with a glial dysfunction etiology. As reported in the Nov 26 Nature Communications, by screening for suppressors and enhancers of glial toxicity, the team honed in on nitric oxide (NO) signaling. The researchers confirmed their findings in a mouse model of the disease, as well as in brain tissue from patients. These findings point to a central mechanism contributing to glial-induced neuronal death in Alexander disease, and could shed light on other degenerative diseases linked to astrocyte dysfunction.
Wang L, Hagemann TL, Kalwa H, Michel T, Messing A, Feany MB. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nat.Commun. 2015 Nov 26;6:8966.[Pubmed]