Researchers have discovered how genetic
mutations linked to Parkinson’s disease might play a key role in the death of
brain cells, potentially paving the way for the development of more effective
In the new study, published in Nature Neuroscience, a team of
researchers from UCL, the University of Cambridge and the University of
Sheffield showed how defects in the Parkinson’s gene Fbxo7 cause problems with ‘mitophagy’ – an essential process
through which our bodies are able to get rid of damaged cells.
Mitochondria are the ‘energy
powerhouses’ of cells. Their
function is vital in nerve cells which require a great deal of energy in order
to function and survive. Dysfunctional mitochondria are
potentially very harmful and, normally, cells dispose of the damaged
mitchondria by self-eating them, a process called mitophagy.
of what we know about the mitophagy process comes from the study of the
familial forms of Parkinson’s, one of the most common diseases of
the brain. Over the last
three years, two genes associated with familial Parkinson’s disease,
PINK1 and Parkin, have been reported to play a role in mitophagy.
These findings suggest that treatment strategies that target mitophagy might be developed to benefit patients with Parkinson's disease in the future.
Dr Helene Plun-Favreau, UCL Institute of Neurology
new study shows just how central the role of mitophagy is and how mutations
in Fbxo7 are also linked with the
disease and interfere with the PINK1-Parkin pathway. In people with
Parkinson’s, genetic mutations cause defects in mitophagy, leading to a build-up of dysfunctional
mitochondria. This is likely to explain, at least partially, the
death of brain cells in Parkinson’s patients with these mutations.
of the lead authors, Dr Helene Plun-Favreau from the UCL Institute of
Neurology, said: “These findings suggest that treatment strategies that target
mitophagy might be developed to benefit patients with Parkinson's disease in
Plun-Favreau, who was recently awarded a grant from the National Institute for
Health Research (NIHR) University College London Hospitals Biomedical Research
Centre, said: “What makes the study so robust is the confirmation of defective
mitophagy in a number of different Parkinson’s models, including cells of
patients who carry a mutation in the Fbxo7
Dr Heike Laman, University of Cambridge, said: "This research focuses the
attention of the PD community on the importance of the proper maintenance of
mitochondria for the health of neurons. We are really only at the very
beginning of this work, but perhaps we can use this information to enable
earlier diagnosis for Parkinson’s disease patients or design therapies aimed at
supporting mitochondrial health."
Nicholas Wood, Neuroscience programme director for the NIHR University College
London Hospitals BRC, said: “It is very exciting to see how detailed biological
work of this type can highlight a single pathway that contributes to Parkinson’s
disease. This presents the opportunity of more rationale drug design for many
forms of parkinsonism.”
Hugh Perry, chair of the Neurosciences and Mental Health Board at the Medical
Research Council who part-funded the study, said: “This study raises
interesting questions about precisely how brain cells die in a Parkinson’s
patient: the process which is key to understanding the disease’s
progression. The more we understand
about the basic molecular events which contribute to the onset and progression
of Parkinson’s disease, the better placed we will be to develop treatments to
stop it in its tracks.”
The work was funded by the Medical Research
Council, the Wellcome Trust and The NIHR Biomedical Research Centre at University College London Hospitals NHS
Foundation Trust and University College London.
Media contact: David Weston