Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.12.090688v1?rss=1 Authors: Morshed, N., Ralvenius, W. T., Nott, A., Watson, L. A., Rodriguez, F. H., Akay, L. A., Joughin, B. A., Pao, P.-C., Penney, J., LaRocque, L., Mastroeni, D., Tsai, L.-H., White, F. M. Abstract: Alzheimer's disease (AD) is characterized by the appearance of amyloid-beta plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK-p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec-F which was upregulated on a subset of reactive microglia. The human paralog Siglec-8 was also upregulated on microglia in AD. Siglec-F and Siglec-8 were upregulated following microglial activation with interferon gamma (IFNg) in BV-2 cell line and human stem-cell derived microglia models. Siglec-F overexpression activates an endocytic and pyroptotic inflammatory response in BV-2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine-based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV-2 cells. Collectively, our results point to an important role for mouse Siglec-F and human Siglec-8 in regulating microglial activation during neurodegeneration. Copy rights belong to original authors. Visit the link for more info