Wolfson Institute for Biomedical Research



Professor Stuart Pickering-Brown

WIBR Seminar

'Recent progress in understanding the mechanism of frontotemporal lobar degeneration'

Professor Stuart Pickering-Brown

(Institute of Brain, Behaviour and Mental Health, University of Manchester)

Host: professor David Sattelle

Frontotemporal lobar degeneration (FTLD) is now recognized as an important cause of neurodegenerative disease, often in people below the age of 65.  FTLD has a high incidence of inheritance with up to 40% of patients having a family history of disease.  Much progress has been made in recent times in our understanding of the genetics of FTD with several genes being identified as a cause of this disease.  The most common genetic cause of FTLD identified to date is a hexanucleotide expansion in the uncharacterized gene C9orf72.  One of the likely mechanisms contributing to neurodegeneration associated with the expansion are di-peptides that are translated from both reading frames.  These form cytoplasmic and intranuclear inclusions.  In addition, the RNA transcribed from it form intranuclear foci.  We have generated antibodies to all five di-peptide repeats and have also generated expression constructs to model these in vitro.  Our di-peptide expression constructs recapitulate what is observed in patients perfectly, with cytoplasmic and intranuclear inclusions forming within 24 hours of transfection.  These inclusions are also p62, ubiquitin and ubiquilin-2 positive.  We believe these form an excellent model to study one of the mechanisms leading to C9orf72 related neurodegeneration.

Download Poster

Date: Thursday 19th March 2015
Time: 4pm (please arrive 15 mins before start) 
Venue: Cruciform Café, 1st Floor Cruciform Building, Gower Street, UCL, WC1E 6BT
Refreshments will be provided