| First Author | Morshed N | Year | 2020 |
| Journal | Mol Syst Biol | Volume | 16 |
| Issue | 12 | Pages | e9819 |
| PubMed ID | 33289969 | Mgi Jnum | J:355625 |
| Mgi Id | MGI:7748914 | Doi | 10.15252/msb.20209819 |
| Citation | Morshed N, et al. (2020) Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration. Mol Syst Biol 16(12):e9819 |
| abstractText | 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 (IFNgamma) 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. |
