Download TIGAR: a promising new drug target for Parkinson`s research project

TIGAR: a promising
new drug target for
Parkinson’s?
Oliver
Project information
Lead researcher
Dr Oliver Bandmann
Location
University of Sheffield
Cost
£127,840 over 2 years
Start date
April 2013
Type of project
Project grant
Project code
G-1304
Project background
Changes in a gene called PINK1 are linked to rare early onset forms of Parkinson’s.
Oliver and his team are using zebrafish to study how changes in the PINK1 gene cause
Parkinson’s in great detail. Zebrafish with a faulty version of the PINK1 gene have
problems with their energy-producing cell batteries (known as ‘mitochondria’) and slowly
lose dopamine-producing nerve cells.
•
Genetic discoveries have given us vital clues but haven’t yet led to better treatments.
We can now use animal models to study exactly how changes in genes like PINK1 cause
nerve cell death. And this is the most promising strategy for identifying new targets for
treatments that can slow down the progression of Parkinson’s.
•
The team have identified a particular protein called TigarB which is overactive in
their PINK1 mutant zebrafish. Blocking TigarB activity rescues the dopamineproducing cells completely - suggesting that the protein could be a promising new drug
target for Parkinson’s.
•
But there are questions still to answer. Blocking TigarB activity saves dopamineproducing nerve cells in these mutant zebrafish. But it’s not clear how or why TigarB
becomes overactive in the first place, or how this causes dopamine-producing nerve
cells to die. Oliver also wants to find out whether the equivalent protein (called TIGAR)
is overactive in people with Parkinson’s.
What the researchers are doing
Oliver and his team will use their PINK1 zebrafish to investigate the chain of events inside cells
which causes TigarB to become overactive. They will also study how overactive TigarB causes
dopamine nerve cells to die in their zebrafish. In particular, they will investigate how it affects
their energy-producing mitochondria that are thought to be vital to the health of nerve cells.
In the second part of the project, the team will study TIGAR protein in people with Parkinson’s.
They will investigate TIGAR protein levels in skin cells donated by a Parkinson’s patient with
the PINK1 mutation. They will also apply for tissue from the Parkinson’s UK Brain Bank to
investigate TIGAR levels in the affected brain regions of people diagnosed with Parkinson’s at
a young age. This will help us to find out whether the TigarB changes seen in the zebrafish
model are reflective of what happens inside the brains of people with the condition.
How the research will help people with Parkinson’s
We still don’t have any treatments that can slow or stop the development of Parkinson’s. This
project aims to uncover new and promising targets for treatments that could help save the
precious nerve cells lost in the condition and offer hope of a future cure.
-----------------------------------------------------------------------------------------------------------------------Find out more about our research, visit our website: parkinsons.org.uk/research
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