Researchers at King's College London have identified a new gene
linked to nerve function, which could provide a treatment target
for 'switching off' the gene in people with neurodegenerative
diseases such as Parkinson's disease.
Parkinson's disease affects approximately 7-10 million people
worldwide and is characterised by progressive loss of motor
function, psychiatric symptoms and cognitive impairment.
Current treatments for Parkinson's only treat symptoms of the
disease rather than its underlying causes, so these new findings in
fruit flies could lead to novel preventative treatments if
replicated in humans.
Previous research suggests that defects in mitochondria, which
are tiny 'batteries' in cells that provide energy, play an
important role in a number of diseases that affect the nervous
system, including Parkinson's. However, until now the neuronal
processes underlying the development of these conditions were
unknown.
The study discovered that damaged mitochondria in fruit flies
produce a signal which stops nerve cells from working. A gene
called HIFalpha was found to regulate the nerve signals from
damaged mitochondria and, when this gene was 'switched off' by the
research team, nerve function in flies with Parkinson's disease was
restored. By deactivating the HIFalpha gene, the early failure of
nerve cells caused by mitochondrial damage was prevented.
An identical effect was observed in flies with Leigh syndrome, a
rare neurological disorder caused by a severe mitochondrial defect,
which typically arises in the first year of life in humans.
As the HIFalpha gene is also found in humans, this new finding
could pave the way for new treatments in the future, according to
the study authors.
Joseph Bateman from King's College London, said: "Like their
human counterparts flies with Parkinson's disease progressively
lose motor function, which includes a negative impact on their
ability to climb. Remarkably, we found that switching off a
particular gene dramatically improved their motor function and
climbing ability.
"The biggest surprise from our work is that damaged mitochondria
produce a signal that actively prevents nerve cells from working
properly. Thanks to this study we now have a much better
understanding of how nerve cells function, which could transform
the way in which neurological diseases such as Parkinson's are
understood and treated."??
Claire Bale, of Parkinson's UK, said: "Understanding how subtle
changes in our genes may trigger brain cell death is one of the
most promising avenues for the development of new treatments for
Parkinson's.
"This discovery adds a new piece to the intricate jigsaw puzzle
of genetic factors that play a part in Parkinson's."
The paper, Mitochondrial retrograde signalling regulates neuronal
function, is published in the Proceedings of the National
Academy of Sciences.