EFFECTS OF HIGH RISK PARKINSON'S MUTATIONS ARE REVERSIBLE
Researchers from the
University of Sheffield have found vital new evidence on how to target and
reverse the effects caused by one of the most common genetic causes of
Parkinson's.
Mutations in a gene
called LRRK2 carry a well-established risk for Parkinson's disease, however the
basis for this link is unclear.
The team, led by
Parkinson's UK funded researchers Dr Kurt De Vos from the Department of
Neuroscience and Dr Alex Whitworth from the Department of Biomedical Sciences,
found that certain drugs could fully restore movement problems observed in
fruit flies carrying the LRRK2 Roc-COR Parkinson's mutation.
These drugs,
deacetylase inhibitors, target the transport system and reverse the defects
caused by the faulty LRRK2 within nerve cells. The study is published today (15
October 2014) month in Nature Communications.
Dr De Vos, a
Lecturer in Translational Neuroscience at the world-leading Sheffield Institute
for Translational Neuroscience (SITraN), said: "Our study provides
compelling evidence that there is a direct link between defective transport
within nerve cells and movement problems caused by the LRRK2 Parkinson's
mutation in flies."
Co-investigator Dr
Alex Whitworth explained: "We could also show that these neuronal
transport defects caused by the LRRK2 mutation are reversible.
"By targeting
the transport system with drugs, we could not only prevent movement problems,
but also fully restore movement abilities in fruit flies who already showed
impaired movement marked by a significant decrease in both climbing and flight
ability."
The LRRK2 gene
produces a protein that affects many processes in the cell. It is known to bind
to the microtubules, the cells' transport tracks. A defect in this transport
system has been suggested to contribute to Parkinson's disease. The researchers
have investigated this link and have now found the evidence that certain LRRK2
mutations affect transport in nerve cells which leads to movement problems
observed in the fruit fly (Drosophila).
The team then used
several approaches to show that preventing the association of the mutant LRRK2
protein with the microtubule transport system rescues the transport defects in
nerve cells, as well as the movement deficits in fruit flies.
Dr De Vos added:
"We successfully used drugs called deacetylase inhibitors to increase the
acetylated form of α-tubulin within microtubules which does not associate with
the mutant LRRK2 protein. We found that increasing microtubule acetylation had
a direct impact on cellular axonal transport.
"These are very
promising results which point to a potential Parkinson's therapy. However,
further studies are needed to confirm that this rescue effect also applies in
humans."
Dr Beckie Port,
Research Communications Officer at Parkinson's UK, which helped to fund the
study, said: "This research gives hope that, for people with a particular
mutation in their genes, it may one day be possible to intervene and stop the
progression of Parkinson's.
"The study has
only been carried out in fruit flies, so much more research is needed before we
know if these findings could lead to new treatment approaches for people with
Parkinson's.
Parkinson's is a
degenerative neurological condition, for which there currently is no cure. The
main symptoms of the condition are tremor, slowness of movement and rigidity.
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