Researchers have discovered how genetic mutations linked to Parkinsons’s disease may be key to the brain cell death associated with the disease, paving the way for developing more effective drug treatments.
In a new study, published in Nature Neuroscience, BRC-supported researchers along with teams from the University of Cambridge and the University of Sheffield, have shown how genetic defects cause problems with the ‘mitaphagy’ process which is so essential for the body to get rid of defective mitochondria. The researchers also discovered a third gene associated with Parkinson’s disease, Fbxo7.
Mitochondria are the ‘energy powerhouses of the cells’. Their function is vital in nerve cells which require a great deal of energy 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.
Most 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.
This 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 and there is 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.
Lead author Dr Helene Plun-Favreau 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 gene”.
Dr Plun-Favreau, who was recently awarded a grant from the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, said: “These findings suggest that treatment strategies that target mitophagy might be developed to benefit patients with Parkinson's disease.”
Prof Nicholas Wood, Neuroscience programme director for the NIHR University College London Hospitals BRC, commented: “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.”
Dr Heike Laman from the 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 PD patients or design therapies aimed at supporting mitochondrial health.”
This research was published in Nature Neuroscience online on 11 August 2013, to read the full paper click here.
