Researchers Identify New Mutation Link In Parkinson’s Disease

A collaboration between the University College London Institute of Neurology, the University of Cambridge and the University of Sheffield found a new link between genetic mutations associated to Parkinson’s disease (PD). The study entitled “The Parkinson’s disease–linked proteins Fbxo7 and Parkin interact to mediate mitophagy” was published in the journal Nature Neuroscience.

PD affects approximately six million patients worldwide, accounting for the second most common progressive chronic neurodegenerative disorder after Alzheimer’s disease. It causes severe motor dysfunctions (bradykinesia, resting tremor, rigidity and postural instability) but also non-motor symptoms, such as impairment of autonomic function and cognition deficits.

Most PD cases are of “sporadic” origin although 5-10% of patients are known to have familial PD caused by mutations in specific genes. At least nine genes are associated with both autosomal dominant (one of the parents has the mutated gene) and autosomal recessive (both parents have to carry the mutated gene to transmit the disease) PD. Mutations in the genes PINK1 and Parkin lead to autosomal recessive familial forms of PD. They code for proteins involved in clearance of damaged mitochondria, the ‘energy powerhouses’ of cells. The removal of dysfunctional mitochondria, a process known as mitophagy, is essential for proper neuronal function and may contribute to brain cell death in PD patients.

Researchers have now found mutations in the gene encoding F-box only protein 7 (Fbxo7) in families with a severe form of autosomal recessive PD, which also affect mitophagy. “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,” said Helene Plun-Favreau, one of the lead authors of the study in a press release.

Importantly, Fbxo7 mutations interfere with PINK1 and Parkin proteins revealing a common pathway to PD. “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,” explained Heike Laman, study co-author.

Overall, the understanding of basic molecular events that contribute to the onset and progression of PD may reveal a new therapeutic strategies. “These findings suggest that treatment strategies that target mitophagy might be developed to benefit patients with Parkinson’s disease in the future,” concluded Plun-Favreau.