Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.25.061762v1?rss=1 Authors: Massey, A. R., Monogue, B., Chen, Y., Lesteberg, K., Johnson, M. E., Bergkvist, L., Steiner, J., Ma, J., Mahalingam, R., Kleinschmidt-Demasters, B. K., Escobar Galvis, M., Brundin, P., Kunath, T., Beckham, J. D. Abstract: The protein alpha-synuclein (asyn) is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinsons disease (PD); yet, a functional role for asyn in neurons is not clearly established. We have previously shown that asyn expression is up-regulated following viral infection in neurons and may plays a key role in host immune responses to viral infections. Here we systematically characterize a functional role of asyn in the brain and in individual cells in brain tissue. We now show that asyn expression in the brain supports expression of specific interferon-stimulated genes (ISGs) following acute RNA virus infection in neurons. Using pluripotent stem cell-derived human neurons, we show that asyn mediates expression of ISGs following RNA virus infection and following treatment with poly I:C and type 1 interferon. Our results establish a novel functional role for asyn in neuronal innate immunity by a mechanism that promotes interferon-stimulated gene expression. Copy rights belong to original authors. Visit the link for more info