Imperial College London
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DrAlexiNott

Faculty of Medicine, Department of Brain Sciences

Lecturer in Neurogenomics, UK DRI Group Leader
 
 
 
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Contact

 

a.nott Website

 
 
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Location

 

Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Morshed:2020:10.15252/msb.20209819,
author = {Morshed, N and Ralvenius, WT and Nott, A and Watson, LA and Rodriguez, FH and Akay, LA and Joughin, BA and Pao, P-C and Penney, J and LaRocque, L and Mastroeni, D and Tsai, L-H and White, FM},
doi = {10.15252/msb.20209819},
journal = {Mol Syst Biol},
title = {Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration.},
url = {http://dx.doi.org/10.15252/msb.20209819},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Alzheimer's disease (AD) is characterized by the appearance of amyloid-β 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 (IFNγ) 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.
AU  - Morshed,N
AU  - Ralvenius,WT
AU  - Nott,A
AU  - Watson,LA
AU  - Rodriguez,FH
AU  - Akay,LA
AU  - Joughin,BA
AU  - Pao,P-C
AU  - Penney,J
AU  - LaRocque,L
AU  - Mastroeni,D
AU  - Tsai,L-H
AU  - White,FM
DO  - 10.15252/msb.20209819
PY  - 2020///
TI  - Phosphoproteomics identifies microglial Siglec-F inflammatory response during neurodegeneration.
T2  - Mol Syst Biol
UR  - http://dx.doi.org/10.15252/msb.20209819
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33289969
VL  - 16
ER  -
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