Michael A Wheeler, Merja Jaronen, Ruxandra Covacu, Stephanie E J Zandee, Giulia Scalisi, Veit Rothhammer, Emily C Tjon, Chun-Cheih Chao, Jessica E Kenison, Manon Blain, Vijayaraghava T S Rao, Patrick Hewson, Andreia Barroso, Cristina Gutiérrez-Vázquez, Alexandre Prat, Jack P Antel, Russ Hauser, Francisco J Quintana
Genome-wide studies have identified genetic variants linked to neurologic diseases. Environmental factors also play important roles, but no methods are available for their comprehensive investigation. We developed an approach that combines genomic data, screens in a novel zebrafish model, computational modeling, perturbation studies, and multiple sclerosis (MS) patient samples to evaluate the effects of environmental exposure on CNS inflammation. We found that the herbicide linuron amplifies astrocyte pro-inflammatory activities by activating signaling via sigma receptor 1, inositol-requiring enzyme-1α (IRE1α), and X-box binding protein 1 (XBP1)...
January 24, 2019: Cell