Skip Navigation



Human Molecular Genetics Advance Access published online on February 11, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn041
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrowOA All Versions of this Article:
17/11/1527    most recent
ddn041v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Miranda, E.
Right arrow Articles by Lomas, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miranda, E.
Right arrow Articles by Lomas, D. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB

Elena Miranda1,*, Ian McLeod1, Mark J. Davies1, Juan Pérez1,2, Karin Römisch3, Damian C. Crowther1,4 and David A. Lomas1

1 Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, United Kingdom 2 Departamento de Biología Celular, Genética y Fisiología, Universidad de Málaga, Facultad de Ciencias, Campus de Teatinos, Málaga, 29071, España 3 University of Trento, Center for Integrative Biology, via delle Regole, 101, 38100 Mattarello (Trento), Italy 4 Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, United Kingdom

* To whom correspondence should be addressed: e-mail: em285{at}cam.ac.uk, phone: (+44) 1223 336825, Fax: (+44) 1223 336827

Received December 17, 2007; Revised February 7, 2008; Accepted February 7, 2008

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is an autosomal dominant dementia that is characterised by the retention of polymers of neuroserpin as inclusions within the endoplasmic reticulum (ER) of neurons. We have developed monoclonal antibodies that detect polymerised neuroserpin and have used COS-7 cells, stably transfected PC12 cell lines and transgenic Drosophila melanogaster to characterise the cellular handling of all four mutant forms of neuroserpin that cause FENIB. We show a direct correlation between the severity of the disease-causing mutation and the accumulation of neuroserpin polymers in cell and fly models of the disease. Moreover mutant neuroserpin causes locomotor deficits in the fly allowing us to demonstrate a direct link between polymer accumulation and neuronal toxicity.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.