Download Looking for DNA modifications in Parkinson`s (PDF

Nigel
Looking for DNA
modifications in
Parkinson’s
Project information
Lead researcher
Dr Nigel Williams
Location
Cardiff University
Cost
£232,404 over 2 years
Start date
Jan 2016
Type of project
Project grant
Project code
G-1502
Project background
People with Parkinson’s don’t have enough of a chemical called dopamine because some
nerve cells in their brain have died. We don’t yet understand why people get Parkinson’s,
but genes, lifestyle and environmental factors are all thought to be involved.

It’s rare for an individual to develop Parkinson’s solely due to the genes they
inherit – the condition is directly caused by genetic changes in less than 5% of
people. It is more common to inherit subtle changes in certain genes that slightly
increase risk of Parkinson’s. These changes are more common but we are unsure
how they increase the chance of developing Parkinson’s.

Nigel’s team have already investigated molecules that stick to our DNA in
Parkinson’s. As we age, we accumulate molecules on our DNA. This process –
called DNA methylation – is known to play an important part in conditions including
cancer, rheumatoid arthritis and type 2 diabetes. Lifestyle and environmental factors
(like smoking, diet and exposure to toxins) can cause these molecules to
accumulate faster. Nigel has discovered inheriting subtle changes in certain genes
can also affect the accumulation of molecules and increase the risk of developing
Parkinson’s.

There is a second type of DNA modification that may be involved called
histone modification. Our cells contain the same DNA – a full score of instructions
for every cell in our bodies, yet our cells are not all the same. Histone modifications
help make sure the right parts of the DNA are active in the right cells. Like other
modifications, they don’t change the DNA code but they tell the cell how to read it
and can change how active certain genes are. Nigel’s keen to find out whether
these modifications also have role in Parkinson’s by influencing the behavior of
genes linked to the condition.
What the researchers are doing
Nigel and his team will study high quality brain tissue samples donated to the Parkinson’s
UK Brain Bank. Using state-of-the-art technology they will look for differences in the
histone modifications in the areas of the brain that are commonly affected in Parkinson’s
compared to areas that are not affected. They will then look to see whether individuals
who carry a genetic change known to increase risk of Parkinson’s have a different pattern
of histone modification to those without these genetic changes.
How the research will help people with Parkinson’s
Drugs that can enter the brain and reverse histone modification have already been
identified. Should this project identify histone modifications that are linked to Parkinson’s it
could highlight a potential new way to treat the condition. This project has huge potential to
improve our understanding of why some people get Parkinson’s and could lead to
improvements in diagnosis and future treatment.
We’re backing the best and
brightest minds to unlock the
ideas that will lead to new
treatments, and one day a cure
Find out more about our research, visit our website:
parkinsons.org.uk/research
Or contact the Parkinson’s UK research team at:
[email protected]
Parkinson’s UK is the operating name of the Parkinson’s Disease Society of the United Kingdom. A company limited by
guarantee. Registered in England and Wales (948776). Registered office: 215 Vauxhall Bridge Road, London SW1V
1EJ. A charity registered in England and Wales (258197) and in Scotland (SC037554). © Parkinson’s UK, Nov 2012