Gene Linked to Mitochondria May Aid in New Parkinson’s Disease Treatments

A team led by scientists from the King’s College London recently published in the journal Proceedings of the National Academy of Sciences the finding of a gene associated with mitochondrial signaling and nerve function, and which could potentially represent a treatment target for patients with neurodegenerative conditions like Parkinson’s disease.

Mitochondria are key regulators of cellular homeostasis, and mitochondrial dysfunction is known to be strongly linked to neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Mitochondria communicate their bioenergetic status to the cell via a mechanism called mitochondrial retrograde signaling.

To investigate the role of mitochondrial retrograde signaling in neurons, in the study entitled “Mitochondrial retrograde signaling regulates neuronal function,” Dr. Joseph Bateman and colleagues induced mitochondrial dysfunction in the nervous system of Drosophila (the fruit fly). Researchers observed that neuronal mitochondrial dysfunction causes reduced viability, defects in neuronal function, decreased redox potential, and reduced numbers of presynaptic mitochondria and active zones.

Interestingly, the results revealed that damaged mitochondria in fruit flies produced a signal that stopped nerve cells from operating. Researchers observed that the HIF (hypoxia inducible factor)-alpha gene regulated the nerve signals from damaged mitochondria, and that when this gene was “switched off” by the team, the early failure of nerve cells due to mitochondrial damage was stopped and the nerve function in fruit flies with Parkinson’s disease was re-established. A similar effect was also found in flies with Leigh syndrome, a condition caused by a severe mitochondrial defect.

Since the HIF-alpha gene is also present in humans, this new discovery could lead to the development of new treatments.

Dr. Bateman, from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and the study’s senior author, explained in a news release: “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, Head of Research Communications at Parkinson’s UK, concluded, “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 the disease.