Download Helping cells get rid of toxic waste in Parkinson`s

Helping cells get rid
of toxic waste in
Parkinson’s
Sylvie
Project information
Lead researcher
Professor Urbe
Location
University of Liverpool
Cost
£92,339 over 3 years
Start date
January 2016 TBC
Type of project
PhD Studentship
Project code
H-1502
Project background
Changes in the Parkin gene are one of the most common known causes of early-onset
Parkinson’s. And researchers have already discovered much about the role of the Parkin
protein in Parkinson’s.
Parkin is involved in keeping cells healthy by getting rid of waste, such as worn out and
broken proteins or parts of the cell. This waste disposal process is called autophagy and
getting rid of toxic waste is essential for the survival of the cell. Both normal aging and
neurological conditions – such as Parkinson’s – have been linked to slower autophagy.
We know that Parkin is responsible for tagging waste so it can bagged up and taken to the
waste disposal. By tagging proteins, Parkin helps to speed up autophagy. Changes in the
Parkin gene can mean the protein doesn’t work properly, which causes autophagy to slow
down and toxic waste to build up.
One of the parts of the cell that Parkin helps to remove when broken is the mitochondria.
Mitochondria are like batteries – they produce all the energy the cell needs – but when
they get old or damaged they start to produce a lot of toxins that can damage the cell. So
it’s essential that cells keep repairing and replacing them.

In cells where ever there is an accelerator, like Parkin, there is normally a
brake. Professor Urbe’s team are experts in a family of proteins which removes
tags from proteins. These proteins are called deubiquitylases, or DUBs. The team
believe that DUBs normally provide the brake to slow down the cell processing
system.

In Parkinson’s, when Parkin isn’t work properly, easing off on the brake may
help speed up the cell’s processing system. The team plan to test compounds
that turn off DUBs to see if they could work in Parkinson’s.
What the project will do
This project is a studentship. The team plan to provide an excellent training environment,
and experience using various techniques, to help a promising student start a career in
Parkinson’s research.
As there are approximately 90 different DUBs in the human genome, the student will first
identify which DUBs are involved in putting the brakes on the removal of damaged
mitochondria. Next the student will build on previous research that suggests a DUB called
USP30 might be a good target. They will next create a new cell model to investigate how
this DUB is involved in removing damaged mitochondria.
Finally, they will test compounds that target DUBs to see if they stop tags being removed
and speed up the removal of broken mitochondria.
How the research will help people with Parkinson’s
This research could identify a new target for developing better treatments for Parkinson’s.
The team hope that, by improving the removal of damaged mitochondria, drugs that target
DUBs could protect the brain cells affected by Parkinson’s.
If this research is successful it would be the first step to identifying a new type of drug that
could one day slow or stop the progression of Parkinson’s.
-----------------------------------------------------------------------------------------------------------------------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