Wolfson Institute for Biomedical Research
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
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 dipeptide 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.
Thursday 19th March 2015
4pm
The Wolfson Institute for Biomedical Research
st
1 Floor Cruciform Building, Cruciform Café
Gower Street
London, WC1E 6BT
alison.kelly@ucl.ac.uk / 020 7679 6134
www.ucl.ac.uk