Imperial College London
Alternate

ProfessorRobertGlen

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Computational Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7912r.glen Website

 
 
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Location

 

362Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ingwersen:2021:10.1038/s41598-021-88090-1,
author = {Ingwersen, T and Linnenberg, C and D'Acunto, E and Temori, S and Paolucci, I and Wasilewski, D and Mohammadi, B and Kirchmair, J and Glen, RC and Miranda, E and Glatzel, M and Galliciotti, G},
doi = {10.1038/s41598-021-88090-1},
journal = {Scientific Reports},
pages = {1--13},
title = {G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic},
url = {http://dx.doi.org/10.1038/s41598-021-88090-1},
volume = {11},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a progressive neurodegenerative disease caused by point mutations in the gene for neuroserpin, a serine protease inhibitor of the nervous system. Different mutations are known that are responsible for mutant neuroserpin polymerization and accumulation as inclusion bodies in many cortical and subcortical neurons, thereby leading to cell death, dementia and epilepsy. Many efforts have been undertaken to elucidate the molecular pathways responsible for neuronal death. Most investigations have concentrated on analysis of intracellular mechanisms such as endoplasmic reticulum (ER) stress, ER-associated protein degradation (ERAD) and oxidative stress. We have generated a HEK-293 cell model of FENIB by overexpressing G392E-mutant neuroserpin and in this study we examine trafficking and toxicity of this polymerogenic variant. We observed that a small fraction of mutant neuroserpin is secreted via the ER-to-Golgi pathway, and that this release can be pharmacologically regulated. Overexpression of the mutant form of neuroserpin did not stimulate cell death in the HEK-293 cell model. Finally, when treating primary hippocampal neurons with G392E neuroserpin polymers, we did not detect cytotoxicity or synaptotoxicity. Altogether, we report here that a polymerogenic mutant form of neuroserpin is secreted from cells but is not toxic in the extracellular milieu.
AU  - Ingwersen,T
AU  - Linnenberg,C
AU  - D'Acunto,E
AU  - Temori,S
AU  - Paolucci,I
AU  - Wasilewski,D
AU  - Mohammadi,B
AU  - Kirchmair,J
AU  - Glen,RC
AU  - Miranda,E
AU  - Glatzel,M
AU  - Galliciotti,G
DO  - 10.1038/s41598-021-88090-1
EP  - 13
PY  - 2021///
SN  - 2045-2322
SP  - 1
TI  - G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-021-88090-1
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000642742500097&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41598-021-88090-1
UR  - http://hdl.handle.net/10044/1/93848
VL  - 11
ER  -
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